Molecular glues can shield insulin-producing cells from diabetes-related damage

 Researchers from the Icahn School of Medicine at Mount Sinai in New York have discovered a novel approach to protecting insulin-producing beta cells from the damaging effects of glucolipotoxicity—a harmful condition linked to the progression of type 2 diabetes (T2D). These findings, published on March 2, 2025 in Nature Communications, could lead to promising treatments targeting beta cell dysfunction.

For patients, this research could lead to new treatments that protect the insulin-producing cells in the pancreas, potentially slowing or even preventing the progression of diabetes, thus reducing the need for insulin therapy and improving long-term blood sugar control. Unlike current therapies that primarily manage blood sugar levels, this approach would allow doctors to directly target beta cell loss, which could improve long-term disease outcomes for their patients.

"This is an exciting step forward in our understanding of beta cell protection and the prevention of diabetes deterioration," said lead author Liora S. Katz, Ph.D.-Associate Professor of Medicine (Endocrinology, Diabetes and Bone Disease) at the Icahn School of Medicine. "For the first time, we've shown that it's possible to use small molecules to fine-tune carbohydrate response element binding protein (ChREBP) activity in a way that could have major therapeutic implications."

More than 500 million people worldwide are living with diabetes, a disease characterized by high blood sugar levels due to insulin resistance and/or beta cell failure. In T2D, long-term exposure to high glucose and fatty acid levels (glucolipotoxicity) can ultimately lead to beta cell dysfunction and death.

ChREBP is a transcription factor that plays a crucial role in regulating glucose metabolism. It exists in two main isoforms: ChREBPα and ChREBPβ. This is the first study to identify and develop small molecules—termed "molecular glues"—that enhance the interaction between ChREBPα and 14-3-3 proteins in pancreatic beta cells.

SAR around analog 1 results in improved stabilizer 30. Credit: Nature Communications (2025). DOI: 10.1038/s41467-025-57241-7

The molecular glues in this case increase the binding between 14-3-3 proteins and ChREBPα, which is anchored in the cytoplasm of the beta cell by the 14-3-3 proteins. Under conditions of glucolipotoxicity, ChREBPα goes into the nucleus and starts making too much of ChREBPβ, which acts to disable and even kill the patient's beta cells. By using a molecular glue designed to increase the binding of ChREBPα to 14-3-3 proteins, ChREBPα never leaves the cytoplasm, cannot enter the nucleus, and therefore does not make ChREBPβ.

When tested in primary human beta cells, these molecular glues significantly reduced the toxic effects of glucolipotoxicity, thus preserving beta cell function and identity. This discovery represents a major shift in diabetes research, as transcription factors like ChREBP have long been considered "undruggable" targets. The study also highlights the broader potential of molecular glues for modulating similar interactions in other diseases.

"Our findings suggest a completely new strategy for preserving beta cell function in diabetes," said Donald K. Scott, Ph.D., Professor of Medicine (Endocrinology, Diabetes and Bone Disease) at the Icahn School of Medicine. "This approach could complement existing diabetes treatments and help prevent disease progression."

Researchers are now working to refine these compounds and evaluate their potential for clinical translation. Future studies will focus on optimizing the molecular glues for therapeutic use and testing them in preclinical diabetes models.

This study was done in collaboration with research teams from Eindhoven University of Technology in the Netherlands and the University of Duisburg-Essen in Germany.

More information: Liora S. Katz et al, Molecular glues of the regulatory ChREBP/14-3-3 complex protect beta cells from glucolipotoxicity, Nature Communications (2025). DOI: 10.1038/s41467-025-57241-7

https://medicalxpress.com/news/2025-03-molecular-shield-insulin-cells-diabetes.html

New consensus report on anaphylaxis: A major advancement in allergy care

 A groundbreaking consensus report on anaphylaxis—the severe reaction some people experience from bee stings, peanut butter exposures, medications, and the like—has been released by the Global Allergy and Asthma Excellence Network (GA2LEN) and recently published in The Journal of Allergy and Clinical Immunology.

The report, developed by an international panel of leading medical experts and patient advocacy organizations, aims to standardize the often-differing definitions of anaphylaxis and teach people how to recognize and manage the condition.

"Many people, including young children and adults, carry epinephrine-injectors (aka epi-pens) to self-treat if an emergency occurs. Many others do not. Likewise, our sprawling medical system, from first responders to hospital emergency staff, does not consistently follow guidelines for diagnosing and treating anaphylaxis. This is partly because no uniform guidelines are used internationally to define, recognize and treat anaphylaxis. That's what this report seeks to address," says Tim Dribin, MD, an emergency medicine expert at Cincinnati Children's and the study's co-chair who devoted a year to leading the group that produced the new standards.

"This tool includes updated clinical criteria to help diagnose anaphylaxis, criteria for using and dosing intramuscular epinephrine, and much more. Importantly, this is the first tool to include distinct infant findings to improve anaphylaxis management in young children," Dribin says.

Burden of anaphylaxis

Anaphylaxis is a constant burden to patients and caregivers around the world. At any moment, thousands of people encounter situations that could cause severe allergic reactions, with symptoms including hives, swollen lips and tongue, difficulty breathing, wheezing, vomiting, and passing out. While fatalities are rare, successful outcomes require rapid recognition and treatment.

Epinephrine is the only proven anaphylaxis treatment to reduce the risk of hospitalization and death. However, only 21% of children and 7% of adults experiencing anaphylaxis receive epinephrine in the community. Additionally, epinephrine underuse in emergency departments is well-documented.

Expert collaboration

The new report reflects the efforts of a 46-member panel of experts from 14 countries and seven medical specialties. The findings have received endorsements from 34 medical and patient advocacy organizations. The National Institutes of Health, the U.S. Food and Drug Administration, and the European Medicines Agency all participated in the study.

"The clinical support tool is a game-changer in anaphylaxis management," says Hugh Sampson, MD, an internationally renowned food allergy and anaphylaxis expert at Mount Sinai School of Medicine and the study's chair. "By improving the rate of epinephrine use, we can significantly reduce the risk of severe reactions and fatalities, ultimately saving lives. The report will also be instrumental for advancing cutting edge research to improve the care and outcomes of patients with anaphylaxis."

"I believe the elements of this report will help ensure that patients around the world receive timely and appropriate treatment, potentially saving lives," says Antonella Muraro, MD, Ph.D., an internationally renowned pediatric allergist at the University of Padova in Italy and the study's co-chair. "The report will be invaluable to first responders, emergency department providers, hospital providers, and allergists, as well as researchers trying to better understand and manage this serious and burdensome condition."

Key highlights of the report include:

1. Unified Definition: The report introduces a new, widely agreed upon definition of anaphylaxis, emphasizing its potential to cause death and detailing the involved organ systems. This definition is designed to be easily understood by health care professionals and the general public to promote improved awareness of anaphylaxis.
2. Educational Overview: An innovative educational tool for health care professionals from different medical fields, training backgrounds, and experience levels. The overview provides essential information on recognizing and managing anaphylaxis, including common causes, symptoms, timely treatment with epinephrine, and key concepts for managing life-threatening reactions.
3. Clinical Support Tool: A new clinical support tool will help health care providers diagnose and treat anaphylaxis. This tool includes updated clinical criteria, indications, and dosing for intramuscular epinephrine and common findings from the different anaphylaxis organ systems. It is the first tool to include distinct infant findings to improve anaphylaxis management in young children, benefiting health care providers not accustomed to caring for children.

More information: Timothy E. Dribin et al, Anaphylaxis definition, overview, and clinical support tool: 2024 consensus report, Journal of Allergy and Clinical Immunology (2025). DOI: 10.1016/j.jaci.2025.01.021

https://medicalxpress.com/news/2025-03-consensus-anaphylaxis-major-advancement-allergy.html

Brain waves measured in sleep predict cognitive impairment years before symptoms, study finds

 Mass General Brigham researchers have developed an AI tool that analyzes brain wave activity recorded during sleep using electroencephalography (EEG), a non-invasive technique that measures electrical activity in the brain through sensors placed on the scalp. The AI tool was developed using sleep study data from a group of women over 65, who were tracked for five years.

The researchers identified subtle differences in brain wave patterns that predicted which participants would later be diagnosed with cognitive impairment. Published in the Journal of Alzheimer's Disease, the study suggests that wearable EEG devices could help identify individuals at risk for dementia, paving the way for earlier interventions.

"Using novel sophisticated analyses, advanced information theory tools, and AI, we can detect subtle changes in brain wave patterns during sleep that signal future cognitive impairment, offering a window of opportunity for intervention years before symptoms appear," said lead author Shahab Haghayegh, Ph.D., a member of the Department of Anesthesia, Critical Care, and Pain Medicine at Massachusetts General Hospital, a founding member of the Mass General Brigham health care system, and Harvard Medical School.

Haghayegh and colleagues analyzed data that was collected for a separate trial on fracture risk in women. For that study, women aged 65 and older underwent a series of cognitive tests around the same time they participated in a sleep study, which included an overnight EEG. Researchers focused on 281 of the participants who had normal cognitive functioning at the time of the initial sleep study and repeated the same cognitive tests five years later. By that second series of assessments, 96 of these women had developed cognitive impairment.

They then applied state-of-art information theory techniques to extract brainwave patterns from the EEG data collected during the sleep study. Using AI, the researchers found that among people who went on to show signs of cognitive impairment, there were changes in subtle brain wave features before symptoms occurred, especially in gamma band frequencies in deep sleep. The AI tool successfully identified 85% of individuals who later developed cognitive impairment, with an overall accuracy of 77%.

The researchers say these findings could help identify patients years before cognitive impairment takes place and suggests a future where wearable EEG devices could become a powerful tool in predicting cognitive decline. Early detection could provide valuable time for individuals to access treatments and make lifestyle modifications that may help maintain cognitive health.

The authors note that further research is necessary to validate these findings across broader populations, including in males and more diverse populations, to verify the link between altered gamma wave activity during deep sleep and future cognitive impairment.

A limitation of the study is that it relied on data from a single night of sleep. However, senior author Kun Hu, Ph.D., physiologist in the Division of Sleep and Circadian Disorders at Brigham and Women's Hospital and Harvard Medical School, notes that EEG data from multiple nights of sleep could be even more predictive of future cognitive impairment.

"The new, FDA-approved treatments for Alzheimer's disease are effective at the earlier stages of dementia, but not the more advanced stages," said Hu. "Interventions that are performed even earlier—before someone shows signs of cognitive decline—are likely to be even more effective."

The research also opens up another exciting possibility, suggesting that manipulating brain electrical activity during sleep could reduce the risk of cognitive decline. Haghayegh and Hu are currently designing a clinical study that will assess if electrical stimulation can alter EEG patterns in sleep and thereby slow down cognitive decline.

"What makes this research particularly significant is how we can identify those at risk using a simple overnight EEG recording," says Haghayegh. "This could completely change how we approach dementia prevention."

More information: Shahab Haghayegh et al. Predicting future risk of developing cognitive impairment using ambulatory sleep EEG: Integrating Univariate Analysis and Multivariate Information Theory Approach, Journal of Alzheimer's Disease (2025). DOI: 10.1177/13872877251319742

https://medicalxpress.com/news/2025-03-brain-cognitive-impairment-years-symptoms.html

'Scientists observe that smartphone restriction for three days can alter brain activity'

 A smartphone's glow is often the first and last thing we see as we wake up in the morning and go to sleep at the end of the day. It is increasingly becoming an extension of our body that we struggle to part with. In a recent study in Computers in Human Behavior, scientists observed that staying away from smartphones can even change one's brain chemistry.

The researchers recruited young adults for a 72-hour smartphone restriction diet where they were asked to limit smartphone use to essential tasks such as work, daily activities, and communication with their family or significant others.

During these three days, the researchers conducted psychological tests and did brain scans using functional magnetic resonance imaging (fMRI) to examine the effects of restricting phone usage. Brain scans showed significant activity shifts in reward and craving regions of the brain, resembling patterns seen in substance or alcohol addiction.

There is an ongoing debate about the term "smartphone addiction" (SPA) making an appearance in many psychological tests, as experts believe that this term might create an inaccurate image of the complex emotional, mental and social aspects associated with smartphone overuse. Nevertheless, neuroscience has seen a growing focus on excessive smartphone use (ESU) due to its association with negative physical and mental health effects, and its links to addictive behaviors.

For this study, 25 young adults aged 18 to 30 who regularly used smartphones were selected. Before the 72-hour restriction period, participants were screened for the severity of physical, psychological, and social issues related to smartphone use and computer gaming, as well as to ensure they did not have any existing mental health conditions.

To assess their mood, smartphone habits, and cravings, participants completed two questionnaires before their first brain scan. They were then instructed to limit phone use for the next 72 hours.

After the three-day restriction period, participants underwent fMRI scans while being shown different sets of images: neutral scenes (such as landscapes and boats), smartphones turned on, and smartphones turned off.

The scans revealed that limiting smartphones led to brain activity changes in areas associated with dopamine and serotonin—neurotransmitters that regulate mood, emotions and also addiction.

The researchers noted that smartphone restriction can resemble withdrawal from addictive substances or even food cravings in some ways, which was noticeable in both heavy (ESU) and regular smartphone (non-ESU) participants.

As technology advances, recognizing how our smartphone usage habits affect our brains is crucial for building healthier digital routines.

More information: Mike M. Schmitgen et al, Effects of smartphone restriction on cue-related neural activity, Computers in Human Behavior (2025). DOI: 10.1016/j.chb.2025.108610

https://medicalxpress.com/news/2025-03-scientists-smartphone-restriction-days-brain.html

Dem Rep. Al Green wields cane, booted from Trump’s address

 Democratic Rep. Al Green of Texas repeatedly interrupted President Trump early on during his speech to the joint session of Congress, waving around his cane and shouting at the commander in chief.

Initially, Trump tried to speak over him, but Green, 77, persisted, shouting, “You don’t have a mandate” — an apparent reference to the budget resolution that narrowly passed the House last week.

Green, who represents a district in the Houston area, also pointed his finger at Trump. On a few occasions, he briefly quieted down to let Trump speak so that he could interject again. 

Republicans seated on the other side of the chamber quickly hit back with chants of “USA,” seeking to drown him out.  

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Rep. Al Green (D-Texas) shouts as President Donald Trump speaks during an address to a joint session of Congress Tuesday night.AFP via Getty Images

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Green heckled Trump during his address to Congress.AP

A House chamber staffer went over to Green to quiet him down, but the Texas rep persisted.

“Remove this gentleman from the chamber!” one Republican shot back, while other GOPers were heard telling Green “sit your a– down.”

Speaker Mike Johnson (R-La.) then intervened and warned Green, to no avail.

“I now direct the Sergeant at Arms to restore order! Remove this gentleman from the Chamber!” Johnson declared.

Finally, Green was escorted out by the House sergeant-at-arms.

Outside the House chamber, Green slammed Trump and accused the president of fomenting “incivility against our civility.”

“It’s worth it to let people know that there are some people who are going to stand up” to Trump, Green told the White House press pool after his ouster.

Presidential speeches before a joint session of Congress have previously faced disruptions from members. 

Three years ago, Reps. Marjorie Taylor Greene (R-Ga.) and Lauren Boebert (R-Col.) heckled former President Joe Biden during his address to Congress. 

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Green is removed from the chamber as Trump addresses a joint session of Congress.Getty Images

House Minority Leader Hakeem Jeffries (D-NY) had reportedly asked his members not to make too much of a scene during the president’s address. 

Multiple Democratic lawmakers skipped the speech and several members waved around signs that said “Save Medicaid” in protest of the president. 

Many Democratic female lawmakers also wore pink in protest of the president. 

During a portion of Trump’s speech when he rattled through some of the Department of Government Efficiency’s purported savings, several Democrats shouted that he was a “liar.” 

At one point, Trump took a dig at Democrats for their animosity toward him. 

“I look at the Democrats in front of me, and I realize there is absolutely nothing I can say to make them happy or to make them stand or smile or applaud, nothing I can do,” Trump chided at one point.

“I could find a cure to the most devastating disease, a disease that would wipe out entire nations or announce the answers to the greatest economy in history or the stoppage of crime to the lowest levels ever recorded,” Trump went on. 

“And these people sitting right here will not clap, will not stand, and certainly will not cheer for these astronomical achievements.”

https://nypost.com/2025/03/04/us-news/dem-rep-al-green-wields-cane-booted-from-trumps-address-to-congress-after-raucous-delay/

Trump says Japan and South Korea want to partner with the US in Alaska pipeline

 U.S. President Donald Trump is set to say Tuesday that Korea, Japan and other countries want to be partners as his administration is working on a natural gas pipeline in Alaska, according to excerpts of his planned address to a joint session of Congress.

The White House released the excerpts before Trump's first address to the joint session since his second presidential term began in January.

"My administration is also working on a gigantic natural gas pipeline in Alaska, among the largest in the world, where Japan, Korea, and other nations want to be our partner — with trillions of dollars being spent by them. It will truly be spectacular," he was to say.

https://www.koreatimes.co.kr/www/nation/2025/03/113_393450.html

Dem lawmaker confronts Trump, is removed from House chamber during address to Congress

 A Democratic U.S. representative was removed from the House chamber after disrupting President Donald Trump’s address to Congress.

“The presidential election of Nov. 5 was a mandate like has not been seen in many decades,” Trump said as he began his speech Tuesday night.

“You have no mandate,” Democratic U.S. Rep. Al Green, of Texas, countered.

Republicans quickly jumped to their feet with chants of “USA! USA!”

Republican members cheered at his removal, shouting “Get out!” and “Goodbye!” at the lawmaker.

Green shouted, “You have no mandate to cut Medicaid!” at Trump before police escorted him from the chamber.

https://www.kbtx.com/2025/03/05/democratic-lawmaker-confronts-trump-is-removed-house-chamber-during-address-congress/