Purdue researchers create biocompatible nanoparticles to enhance systemic delivery of cancer immunotherapy

Purdue University researchers are developing and validating patent-pending nanoparticles (left) to enhance immunotherapy effects against tumors. The nanoparticles are modified with adenosine triphosphate, or ATP, to recruit dendritic cells (right), which are immune cells that recognize tumor antigens and bring specialized immune cells to fight off tumors.
Image Credit: Yoon Yeo

Purdue University researchers are developing and validating patent-pending poly (lactic-co-glycolic acid), or PLGA, nanoparticles modified with adenosine triphosphate, or ATP, to enhance immunotherapy effects against malignant tumors.

The nanoparticles slowly release drugs that induce immunogenic cell death, or ICD, in tumors. ICD generates tumor antigens and other molecules to bring immune cells to a tumor’s microenvironment. The researchers have attached ATP to the nanoparticles, which also recruits immune cells to the tumor to initiate anti-tumor immune responses. 

Yoon Yeo leads a team of researchers from the College of Pharmacy, the Metabolite Profiling Facility in the Bindley Bioscience Center, and the Purdue Institute for Cancer Research to develop the nanoparticles. Yeo is the associate department head and Lillian Barboul Thomas Professor of Industrial and Molecular Pharmaceutics and Biomedical Engineering; she is also a member of the Purdue Institute for Drug Discovery and the Purdue Institute for Cancer Research.

The researchers validated their work using paclitaxel, a chemotherapy drug used to treat several types of cancers. They found that tumors grew slower in mice treated with paclitaxel enclosed within ATP-modified nanoparticles than in mice treated with paclitaxel in non-modified nanoparticles.

“When combined with an existing immunotherapy drug, the ATP-modified, paclitaxel-loaded nanoparticles eliminated tumors in mice and protected them from rechallenge with tumor cells,” Yeo said.

Researchers discover molecule that promotes production of cancer cells in triple-negative breast cancer

Hiroshima University researchers found that AIbZIP is highly upregulated in triple negative breast cancer (TNBC). AIbZIP induces hyper proliferation of TNBC cells by promoting the degradation of p27, a negative regulator for cell proliferation.
Illustration Credit: Atsushi Saito/Hiroshima University

A team of researchers from Hiroshima University has discovered a molecule that promotes the production of cancer cells. This molecule may prove to be a potential therapeutic target in the treatment of triple-negative breast cancer, an aggressive form of breast cancer.

Breast cancer is the most common type of cancer, ranking fifth among all cancers in cancer-related deaths. In 2020, there were 2.3 million new cases of breast cancer reported around the globe. In that year, breast cancer caused 685,000 deaths.

Several studies have reported that a molecule called AIbZIP (androgen induced basic leucine zipper) promotes malignant behavior in different cancer types. So, the research team examined the potential role of AIbZIP in malignant tumors. Their computer simulation analysis revealed that AIbZIP was highly expressed in the luminal androgen receptor subtype of triple negative breast cancer, playing a significant role in cell cycle regulation. They identified a novel mechanism by which AIbZIP regulates cancer cell proliferation in this type of breast cancer.

“We found that AIbZIP is highly upregulated in triple negative breast cancer. AIbZIP plays a crucial role for hyper proliferation of triple negative breast cancer cells by promoting the degradation of p27, a negative regulator for cell proliferation. Our study indicates that AIbZIP may be potential therapeutic target of triple negative breast cancer” said Atsushi Saito, an associate professor and Kazunori Imaizumi, a professor in the Department of Biochemistry, Graduate School of Biomedical and Health Sciences, Hiroshima University.  

Assessing the impact of sweeteners on appetite

Stevia
Photo Credit: Jan Haerer

Replacing sugar with artificial and natural sweeteners in foods does not make people hungrier – and also helps to reduce blood sugar levels, a significant new study has found. 

The double blind randomized controlled trial found that consuming food containing sweeteners produced a similar reduction in appetite sensations and appetite-related hormone responses as sugary foods - and provides some benefits such as lowering blood sugar, which may be particularly important in people at risk of developing type 2 diabetes. 

The use of sweeteners in place of sugar in foods can be controversial due to conflicting reports about their potential to increase appetite. Previous studies have been carried out but did not provide robust evidence. 

However, the researchers say their study, which meets the gold standard level of proof in scientific investigation, provides very strong evidence that sweeteners and sweetness enhancers do not negatively impact appetite and are beneficial for reducing sugar intake. The study is published in The Lancet eBioMedicine.  

Our study provides crucial evidence supporting the day-to-day use of sweeteners and sweetness enhancers for body weight and blood sugar control. 

‘Back to the Future’ to Forecast the Fate of a Dead Florida Coral Reef

Alex Modys, Ph.D., diving at the coral death assemblage in Pompano Ridge and digging up a subfossil coral, Orbicella annularis.
Photo Credit: Anton Olenik, Ph.D., Florida Atlantic University

Rising temperatures and disease outbreaks are decimating coral reefs throughout the tropics. Evidence suggests that higher latitude marine environments may provide crucial refuges for many at-risk, temperature-sensitive coral species. However, how coral populations expand into new areas and sustain themselves over time is constrained by the limited scope of modern observations. 

What can thousands of years of history tell us about what lies ahead for coral reef communities? A lot. In a new study, Florida Atlantic University researchers and collaborators provide geological insights into coral range expansions by reconstructing the composition of a Late Holocene-aged subfossil coral death assemblage in an unusual location in Southeast Florida and comparing it to modern reefs throughout the region. 

Located off one of the most densely populated and urbanized coastlines in the continental United States, the Late Holocene coral death assemblage known as “Pompano Ridge,” records a northward range expansion of tropical coral communities that occurred during a period of regional climate warming more than 2,000 years ago.

Could this happen again in the face of climate change? Going “back to the future,” this study offers a unique glimpse into what was once a vibrant coral reef assemblage and explores if history can repeat itself.

‘Exhausted’ immune cells in healthy women could be target for breast cancer prevention

Photo Credit: Angiola Harry

Everyone has BRCA1 and BRCA2 genes, but mutations in these genes - which can be inherited - increase the risk of breast and ovarian cancer.

The study found that the immune cells in breast tissue of healthy women carrying BRCA1 or BRCA2 gene mutations show signs of malfunction known as ‘exhaustion’. This suggests that the immune cells can’t clear out damaged breast cells, which can eventually develop into breast cancer.

This is the first time that ‘exhausted’ immune cells have been reported in non-cancerous breast tissues at such scale - normally these cells are only found in late-stage tumors.

The results raise the possibility of using existing immunotherapy drugs as early intervention to prevent breast cancer developing, in carriers of BRCA1 and BRCA2 gene mutations.

The researchers have received a ‘Biology to Prevention Award’ from Cancer Research UK to trial this preventative approach in mice. If effective, this will pave the way to a pilot clinical trial in women carrying BRCA gene mutations.

“Our results suggest that in carriers of BRCA mutations, the immune system is failing to kill off damaged breast cells - which in turn seem to be working to keep these immune cells at bay,” said Professor Walid Khaled in the University of Cambridge’s Department of Pharmacology and Wellcome-MRC Cambridge Stem Cell Institute, senior author of the report.

Magnetic Avalanche Triggered by Quantum Effects

Christopher Simon holds a crystal of lithium holmium yttrium fluoride.
Photo Credit: Lance Hayashida/Caltech

Iron screws and other so-called ferromagnetic materials are made up of atoms with electrons that act like little magnets. Normally, the orientations of the magnets are aligned within one region of the material but are not aligned from one region to the next. Think of groups of tourists in Times Square pointing to different billboards all around them. But when a magnetic field is applied, the orientations of the magnets, or spins, in the different regions line up and the material becomes fully magnetized. This would be like the packs of tourists all turning to point at the same sign.

The process of spins lining up, however, does not happen all at once. Rather, when the magnetic field is applied, different regions, or so-called domains, influence others nearby, and the changes spread across the material in a clumpy fashion. Scientists often compare this effect to an avalanche of snow, where one small lump of snow starts falling, pushing on other nearby lumps, until the entire mountainside of snow is tumbling down in the same direction.

Cats with MDR1 mutation at risk of severe reactions to popular medication

Photo Credit: Zhang Kaiyv

More than half a million cats in the United States could be at risk of a severe or even fatal neurological reaction to the active ingredient in some top-selling parasite preventatives for felines.

While the ingredient, eprinomectin, which is found in products like NexGard COMBO and Centragard, appears safe and effective for the significant majority of cats when used at label doses, a study conducted by Washington State University’s Program for Individualized Medicine identified a risk of severe adverse effects in cats with the MDR1 genetic mutation. Genetically affected cats lack a protective mechanism that prevents certain drugs, including eprinomectin, from entering the brain and causing serious neurological toxicity.

“Almost every week we receive reports about someone’s pet cat having serious reactions to eprinomectin. This is not an issue with the drug itself — the problem lies in the genes of 1% of cats. That is a sizable number considering there are over 60 million pet cats in the U.S., and we’re trying to increase general awareness of these risks,” said Dr. Katrina Mealey, a WSU veterinarian and pharmacologist who led the research.

Patients with delirium more likely to develop dementia

Professor Ruth Hubbard interacting with a patient.
Photo Credit: The University of Queensland

University of Queensland researchers have found older patients who experience delirium are three times more likely to develop dementia.

Professor Ruth Hubbard from UQ’s Centre for Health Services Research (CHSR) said the study also found that every episode of delirium increased the chance of developing dementia by 20 per cent.

“Delirium is an acute confusional state which particularly impacts older people and can have long term detrimental effects on patients,” Professor Hubbard said.

“Our study found that it is also strongly linked to dementia.”

The researchers analyzed a cohort of more than 110,000 patients from New South Wales hospitals over five years.

Lead author and CHSR research fellow, Dr Emily Gordon, said more than 55,000 patients who had experienced delirium were compared to patients who had not.

Rice study identifies protein responsible for gas vesicle clustering in bacteria

Zongru Li (left) and George Lu
Photo Credit: Anna Stafford/Rice University

Gas vesicles are hollow structures made of protein found in the cells of certain microorganisms, and researchers at Rice University believe they can be programmed for use in biomedical applications.

“Inside cells, gas vesicles are packed in a beautiful honeycomb pattern. How this pattern is formed has never been thoroughly understood. We are presenting the first identification of a protein that can regulate this patterning, and we believe this will be a milestone in molecular microbiology,” said George Lu, assistant professor of bioengineering and a Cancer Prevention and Research Institute of Texas scholar.

Lu and colleagues have published their findings in a paper published in Nature Microbiology. The lead author is Zongru Li, a fourth-year bioengineering doctoral student in Lu’s Laboratory for Synthetic Macromolecular Assemblies.

“Gas vesicles are cylindrical tubes closed by conical end caps,” Li said. “They provide buoyancy within the cells of their native hosts.”

Largest ice shelf in Antarctica lurches forward once or twice each day

A side view of the Ross Ice Shelf, the largest ice shelf in Antarctica. Washington University in St. Louis seismologist Doug Wiens discovered that unexpected movements of the Ross Ice Shelf are triggered by the sudden slipping of parts of the Willans Ice Stream.
Photo Credit: Lin Padgham
(CC BY 2.0.)

In Antarctica, heavy glaciers are always on the move. Conveyor belts of ice known as ice streams are the corridors of faster flow that carry most of the vast glaciers’ ice and sediment debris out toward the ocean.

One such ice stream jostles the entire Ross Ice Shelf out of place at least once daily, according to new research from Washington University in St. Louis.

This finding is significant because of the scale of the Ross Ice Shelf: It is the largest ice shelf in Antarctica, about the same size as the country of France.

“We found that the whole shelf suddenly moves about 6 to 8 centimeters (or 3 inches) once or twice a day, triggered by a slip on an ice stream that flows into the ice shelf,” said Doug Wiens, the Robert S. Brookings Distinguished Professor of earth, environmental and planetary science​s in Arts & Sciences. “These sudden movements could potentially play a role in triggering icequakes and fractures in the ice shelf.”

The Ross Ice Shelf is a floating lip of ice that extends out over the ocean from inland glaciers.