Scientists solve the mystery of a brain “switch” that can trigger weight loss in opposite ways

 Cambridge researchers have uncovered why both activating and blocking the same brain receptor can promote weight loss. The findings may help scientists develop obesity treatments that are more effective and potentially work better in combination.

The mouse study, published in Nature Metabolism, found that the outcome depends on which part of the brain is targeted. Activating the receptor in the brainstem reduced appetite, while blocking the same receptor in the hypothalamus produced a similar weight loss effect through a different mechanism.

More than a billion people around the world are living with obesity, a condition that raises the risk of diseases including type 2 diabetes, cardiovascular disease and cancer. Losing weight can reduce some of these risks, but achieving substantial weight loss through diet and exercise alone can be difficult.

How Modern Weight Loss Drugs Target the Brain

A new generation of weight loss medications has emerged in recent years that act on specific receptors involved in appetite. By influencing these receptors, the drugs can reduce food intake, promote weight loss, and help regulate blood sugar.

Several widely used medications, including Wegovy and Ozempic, activate a protein receptor called the glucagon-like peptide 1 receptor (GLP-1R).

Other obesity treatments act on both GLP-1R and another receptor known as the glucose-dependent insulinotropic polypeptide receptor (GIPR). This second target has presented scientists with an unusual puzzle.

Some medications, including Mounjaro and Zepbound, activate GIPR. Others, such as MariTide, block it. Despite producing opposite effects on the same receptor, both approaches can help promote weight loss.

Researchers at the Institute of Metabolic Science, University of Cambridge, set out to understand why. Their experiments in mice revealed that the two types of GIPR drugs work through different regions of the brain. The researchers also found that these approaches can increase weight loss when paired with certain GLP-1-based weight loss medicines.

Tracking GIPR Activity in Different Brain Regions

To identify the brain regions responsible for these effects, the team used genetically engineered mice in which GIPR had been selectively removed from specific areas.

One group lacked GIPR in the brainstem, the region at the base of the brain just above the spinal cord that is involved in appetite and nausea. Another group lacked the receptor in the hypothalamus, an important brain region involved in regulating hunger and body weight. A third group consisted of normal, unmodified mice that served as controls.

Source: ScienceDaily

Scientists uncover the hidden nerve network fueling breast cancer

 New research from the University of Oklahoma has revealed how an aggressive type of breast cancer can manipulate the immune system to draw nerves into tumors, creating conditions that may help the cancer grow.

Scientists have known for years that many solid tumors contain extensive nerve networks. What has been less clear is how those nerves enter the tumor in the first place. The new study, published in Cell Death & Differentiation, provides an explanation for this process in triple-negative breast cancer, a particularly difficult form of the disease to treat.

Immune Cells Help Draw Nerves Into Tumors

The researchers discovered that tumors attract macrophages, a type of immune cell that normally helps the body fight infections and repair damaged tissue. After entering the tumor, these macrophages release brain-derived neurotrophic factor (BDNF), a protein that encourages nearby nerves to grow toward and into the cancer.

BDNF is most widely known for supporting the growth and survival of nerve cells in the brain. In breast cancer, however, the researchers found that tumors can take advantage of this same biological signal. By prompting nerve growth inside the tumor, the process may contribute to cancer progression and resistance to treatment.

"Macrophages are the critical source for drawing nerves into the tumor. Although macrophages typically play a positive role in the body, they are facilitating a negative function in this scenario of breast cancer," said Maureen Cox, Ph.D., an assistant professor in the Department of Microbiology and Immunology at the OU College of Medicine and a research member of OU Health Stephenson Cancer Center.

Blocking the Signal Slowed Tumor Growth

The discovery could open the door to a different way of treating cancer. Instead of focusing only on destroying cancer cells, future therapies might interrupt the signaling between macrophages and the nerves that appear to support tumor growth.

Cox and her colleagues tested this strategy in mice. They used a drug that blocks BDNF signaling and found that nerves no longer grew into the tumors. Tumor growth was also significantly reduced.

"It looks really promising that we can use this drug, which is already on the market, to target BDNF," Cox said. "We believe that the nerves are immunosuppressive, so if we can stop the nerves from growing in the first place, maybe we can boost the immune response to help fight the cancer."

Evidence From Triple-Negative Breast Cancer Patients

The researchers also examined data from people with triple-negative breast cancer to determine whether the same biological pattern might occur in humans. Tumors containing higher levels of macrophages and BDNF were linked with poorer survival, providing evidence that the mechanism observed in mice could also be relevant to patients.

Source: ScienceDaily

Breast cancer is surging among Asian American women — and scientists don’t know why

 A new UC San Francisco-led study has identified a sharp increase in invasive breast cancer among Asian American women over the past two decades.

Breast cancer rates have climbed across nearly every Asian American ethnic group at a pace that exceeds increases seen in any other U.S. ethnic group. The trend is particularly pronounced among women under 50 and among those diagnosed with advanced disease or certain aggressive forms of breast cancer.

Breast Cancer Rates Are Climbing Quickly

The study, published in JAMA Network Open, found that breast cancer incidence rose by more than 3% annually in nearly every Asian American ethnic group examined. The increases were even greater among Chinese and Vietnamese women.

Native Hawaiian women already have some of the highest breast cancer rates among women in the United States. However, their rates increased by about 1% per year, substantially less than the increases observed among Asian American groups.

Researchers say greater use of breast cancer screening probably does not explain the trend. Screening tends to identify more cancers at earlier stages, yet the fastest increases occurred among cancers that had already spread.

One particularly concerning finding involved triple-negative breast cancer, which is considered the most aggressive subtype. Among Chinese American women, cases of triple-negative breast cancer increased by more than 6% each year between 2017 and 2022.

"These patterns are highly concerning from a disparities standpoint," said senior author Scarlett Lin Gomez, PhD, professor of epidemiology and biostatistics at UCSF and co-leader of the Cancer Control Program at the UCSF Helen Diller Family Comprehensive Cancer Center. "They underscore why it is so important to move beyond treating Asian Americans, Native Hawaiians, and Pacific Islanders as a single population."

A Closer Look at Breast Cancer Risk

To examine these trends, researchers analyzed about 150,000 invasive breast cancer cases diagnosed from 2000 through 2022. The data came from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program.

The analysis included nine specific Asian American, Native Hawaiian, and Pacific Islander (AANHPI) populations across 14 states. Together, those states are home to about two-thirds of the U.S. AANHPI population.

Historically, Asian American women, with the exception of Native Hawaiian women, have had lower breast cancer rates than non-Hispanic white women. That difference is now shrinking quickly. By 2022, breast cancer incidence among Asian American women under 50 had become comparable to the rate among white women of the same age group.

Source: ScienceDaily

Scientists turn probiotic bacteria into tiny drug factories for pancreatic cancer

 Cancer immunotherapy has dramatically changed how doctors treat many forms of cancer, yet pancreatic cancer has remained particularly resistant to these advances. A major obstacle is the environment that develops around pancreatic tumors. These tumors often create a "cold" tumor microenvironment that blocks immune cells from launching an effective attack.

Researchers at the University of Chicago have now developed a new approach that could help overcome this problem. In a study published in Science Advances, the team used BifidoSumIL-2, an engineered strain of Bifidobacterium longum, a probiotic bacterium naturally found in the gut, to carry an immune-stimulating treatment directly into tumors.

In animal models, the therapy slowed the growth of pancreatic tumors by selectively activating T cells that fight cancer. Its effects became even stronger when researchers combined it with chemotherapy, radiotherapy or immunotherapy. The findings suggest that BifidoSumIL-2 could eventually provide a new way to improve how pancreatic tumors respond to treatment.

Using Bacteria to Deliver Cancer Therapy

"A big unmet medical need has been pancreatic cancer, and so that was going to be our mountain to climb," said Ralph Weichselbaum, MD, the Daniel K. Ludwig Distinguished Service Professor and Chair of Radiation and Cellular Oncology at the University of Chicago.

BifidoSumIL-2 was created to release a modified version of interleukin-2 (IL-2) once it reaches a tumor. IL-2 is a potent immune signaling molecule that activates T cells involved in attacking cancer. Conventional IL-2 treatment, however, can produce serious side effects and can also stimulate immune cells that actually weaken the antitumor response.

The researchers sought to avoid these problems by using SumIL-2, a modified form of IL-2 engineered to more precisely activate cancer-fighting T cells while reducing stimulation of regulatory T cells. They then placed SumIL-2 inside Bifidobacterium longum so that the therapeutic molecule could be concentrated within tumors instead of throughout the body.

Developing the treatment required scientists from several disciplines to work together, including specialists in microbiology, synthetic biology, oncology, and immunology.

"This was a highly interdisciplinary effort," said Mark Mimee, PhD, Assistant Professor of Microbiology at the University of Chicago. "We had to bring together people who understand bacteria, people who understand tumors, and people who understand the immune system to make something like this possible."

Why Bifidobacterium Can Target Tumors

Bifidobacterium offered the researchers an unusual advantage as a delivery system. The bacterium grows in anaerobic environments, meaning places with very little oxygen. Low oxygen levels are common inside many solid tumors, including pancreatic tumors, while healthy tissues generally contain more oxygen and are therefore less suitable for the bacteria.

Source: ScienceDaily

AI may know how you’ll respond to a vaccine before you get it

 Vaccines prevent serious illness for many people, but the immune protection they produce can differ substantially from one person to another. New research led by Arizona State University offers clues about what may be behind those differences.

The immune system may show signs of how strongly it will react even before vaccination. Researchers at ASU and collaborating institutions examined blood samples from more than 4,000 people, measuring antibodies that recognized 185 antigens. Those immune targets included common viruses and bacteria, along with targets connected to autoimmune diseases.

Artificial intelligence was then used to search for patterns in blood samples taken before and after COVID-19 vaccination. The analysis uncovered antibody signatures that could help separate people who produced strong vaccine responses from those whose responses were weaker.

The findings could eventually contribute to vaccination strategies tailored more closely to an individual's immune system.

"What our study found is that certain biomarkers, when analyzed with AI, can predict who is likely to respond well to a vaccine, even before they receive it. This suggests that some people may be more immune-ready than others," says Joshua LaBaer, who led the study.

LaBaer is executive director of the Biodesign Institute at ASU and director of the Virginia G. Piper Center for Personalized Diagnostics. The project also involved ASU researchers and collaborators from medical and research institutions around the United States.

The study appears in the current issue of the journal Cell Press Blue.

Blood Antibodies May Reveal Vaccine Readiness

Scientists typically evaluate vaccine response after vaccination by measuring whether the immune system generated antibodies against the intended target. In this study, the researchers approached the problem from the opposite direction. They wanted to know whether immune patterns already present in the blood could reveal how someone would respond before receiving a vaccine.

Many factors can influence vaccine response, including age, sex, genetics, previous illnesses and underlying health conditions. People with conditions that compromise the immune system are often more likely to produce weaker responses. However, vaccine outcomes can still vary widely among people who fall into the same general health categories.

The researchers used one of the first approaches to examine a broad antibody "fingerprint" present before vaccination as a measure of immune readiness. While some other prediction strategies depend on genetic testing, this method analyzes antibody patterns in blood, potentially making it easier to translate into clinical practice.

Source: ScienceDaily

This yeast supplement may boost cancer-fighting immunity

 Researchers at Trinity College Dublin and University College Dublin (UCD) have found that a yeast-based dietary supplement can strengthen immune cells involved in fighting cancer in mice.

In experiments with obese laboratory mice, the researchers found that adding the supplement to the animals' diets changed the way immune cells developed and produced stronger cancer-fighting responses.

Obesity can interfere with immune function, making it more difficult for the body to respond effectively to tumors. The new findings suggest that a yeast-based supplement could potentially help restore some of that lost immune activity.

The research was published in the scientific journal Cell Reports. The study was led by Frederick Sheedy, Associate Professor in Immunology in Trinity's School of Biochemistry and Immunology, and Helen Roche, Professor in Nutrigenomics, UCD School of Public Health, Physiotherapy and Sports Science and Director of the UCD Conway Institute.

Training Immune Cells Through Diet

Dr. Anna Ledwith, postdoctoral researcher in Prof. Roche's group and first author of the research paper, said: "We wanted to investigate whether a common dietary supplement, yeast beta-glucan, could reprogram early-stage immune cells in the bone marrow to produce long-lasting, enhanced anti-tumor immune responses.

"Mice were fed a standard or high-fat diet supplemented with yeast beta-glucan for 4-12 weeks, and then their immune system was challenged by different types of cancer cells: colorectal, skin, and breast cancer. The study also tested whether yeast supplementation could overcome immune dysfunction caused by obesity and whether protective effects persist after weight loss."

The researchers wanted to determine whether consuming yeast beta-glucan could produce a form of lasting immune training by changing early immune cells in the bone marrow. They also examined whether the supplement could counter the immune problems caused by obesity.

Prof. Roche said the findings show for the first time that consuming yeast beta-glucan in the diet is enough to trigger trained immunity by altering bone marrow stem cells. Earlier studies achieved similar effects using injections.

Commenting on the significance of the findings, Prof. Roche added: "This is the first demonstration that dietary delivery of yeast beta-glucan is sufficient to induce trained immunity through reprogramming of bone marrow stem cells. Previous research required injections.

"Crucially, this dietary intervention restores anti-tumor innate immunity in obese mice and reverses long-term immune memory defects that persist even after weight loss, a major unmet clinical challenge."

Source: ScienceDaily

This common vitamin was linked to 13% better cognitive scores

 More than 7 million Americans are currently living with Alzheimer's dementia, and that number is expected to climb to nearly 13 million by 2050. New research from Emory University suggests that higher vitamin D supplement intake may be linked to stronger cognitive performance in adults who face an increased risk of developing dementia.

The study included 54 adults with sleep disturbances and mild cognitive impairments (MCI), both of which can be associated with the early stages of dementia. Participants who reported taking at least 5,000 IU of vitamin D each day performed better on measures of cognitive function than those who did not take vitamin D.

Higher Vitamin D Intake Linked to Better Cognitive Scores

The findings, recently published in Sleep Medicine, showed that people taking 5,000 IU or more of vitamin D daily scored more than 13% higher on the Montreal Cognitive Assessment (MoCA) compared with participants who took none, even after researchers adjusted for other factors.

MoCA is a widely used screening test designed to assess memory, thinking skills, and the risk of developing dementia. In contrast to the results seen with the higher intake group, lower daily doses of vitamin D were not associated with improved cognitive scores.

The researchers also highlighted the potential importance of when an intervention takes place. MCI is an intermediate stage between normal cognitive aging and dementia.

"In older adults experiencing both sleep disturbance and mild cognitive impairment, this may represent a critical window for intervention, when cognitive changes are emerging, but opportunities to support brain health may remain," says Victoria Pak, senior author of the study.

"Identifying accessible and modifiable factors, such as vitamin D supplement intake, during the earlier stages of cognitive decline may become increasingly important, particularly as rates of Alzheimer's disease continue to rise," adds Pak, associate professor at Emory University's Nell Hodgson Woodruff School of Nursing.

Vitamin D2 and D3 Showed Similar Results

The researchers also examined whether the form of vitamin D made a difference. Cognitive performance was similar among people taking vitamin D2, which is typically obtained from plants or fungi, and vitamin D3, which the body produces after sun exposure and which can also come from animal-based foods.

Vitamin D is an essential nutrient involved in muscle and nerve function, and it also plays a role in sleep quality and sleep-wake cycles. Sleep problems are common among people with Alzheimer's disease. 50% of those with moderate to severe Alzheimer's disease report sleep disturbances, pointing to a two-way relationship between poor sleep and cognitive decline.

Source: ScienceDaily