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Comment by Dr. Krishna Kumari Challa on August 15, 2025 at 12:31pm

To test out the effect of EPIC1 knockdown, the researchers used "humanized mice"—mice with human immune systems implanted to mimic the effect of the mechanism in a human. Using these mouse models along with RNA interference to knock down EPIC1 in various cancer cell lines, they found that targeting EPIC1 enabled reduced tumor growth and increased T cell and inflammatory macrophage infiltration. This led to a significant improvement in the efficacy of pembrolizumab in TNBC.

"EPIC1 can be a potential therapeutic target in combination with immunotherapy. Coculture assays of T cells or monocytes with cancer cells showed that EPIC1 knockdown could significantly increase the therapeutic effect of pembrolizumab through antitumor T cell and macrophage activation," the researchers write.

This is a promising result, offering hope for more effective treatments for aggressive cancers with limited options. However, the study authors note that these results still need to be tested out in human models and with other types of cancers to determine how best to improve immunotherapy outcomes in the future.

 Dhamotharan Pattarayan et al, The lncRNA EPIC1 suppresses dsRNA-induced type I IFN signaling and is a therapeutic target to enhance TNBC response to PD-1 inhibition, Science Signaling (2025). DOI: 10.1126/scisignal.adr9131

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Part 2

Comment by Dr. Krishna Kumari Challa on August 15, 2025 at 12:30pm

Scientists reverse immunotherapy-resistance by suppressing EPIC1 in mouse model of breast cancer

Immunotherapy employs patients' own immune systems to fight cancer, and it has shown itself to be an effective treatment in many cases. However, some cancers, like triple-negative breast cancer (TNBC), show resistance to immunotherapy. This occurs when tumor cells find ways to evade immune detection—like suppressing immune signaling pathways. One such mechanism is the use of long noncoding RNAs (lncRNAs), which have been found to regulate cancer biology and immune evasion. These lncRNAs render immunotherapies, like the PD-1 inhibitor, pembrolizumab, ineffective.

The good news is that if these mechanisms of immunotherapy-resistance can be identified, scientists may be able to reverse or inactivate them. In a new study, published in Science Signaling, scientists focus on the lncRNA, EPIC1, and its interaction with histone methyltransferase, EZH2, a known contributor of tumor immune evasion in cancer cells.
According to the researchers, they sought to investigate the mechanism by which EPIC1 modulates immune function and determine how it regulates the expression of retroelements (REs)—mobile DNA sequences that produce double-stranded RNA when activated—and dsRNA accumulation in tumor cells.

The researchers found that EPIC1 suppresses the accumulation of cytoplasmic dsRNA and type I interferon (IFN) responses in multiple cancer cell lines, including breast cancer, prostate cancer, and pancreatic cancer. EPIC1 and EZH2 were also shown to work together to repress the expression of immunogenic REs, suggesting a shared pathway for immune evasion.

The study authors write, "Collectively, these results suggest that EPIC1 suppression promotes an antiviral-like type I IFN response with potential antitumor effects."

Comment by Dr. Krishna Kumari Challa on August 14, 2025 at 11:08am

A Case of Bromism Influenced by Use of Artificial Intelligence

Man Hospitalized With Psychiatric Symptoms Following AI Advice

A man who followed a chatbot's health plan ended up in hospital after giving himself a rare form of toxicity.

The story began when the patient decided to improve his health by reducing his intake of salt, or sodium chloride. To find a substitute, he did what so many other people do nowadays: he asked ChatGPT on line.

OpenAI's chatbot apparently suggested sodium bromide, which the man ordered online and incorporated into his diet.

While it is true that sodium bromide can be a substitute for sodium chloride, that's usually if you're trying to clean a hot tub, not to make your fries tastier. But the AI neglected to mention this crucial context.

Three months later, the patient presented to the emergency department with paranoid delusions, believing his neighbour was trying to poison him.

In the first 24 hours of admission, he expressed increasing paranoia and auditory and visual hallucinations, which, after attempting to escape, resulted in an involuntary psychiatric hold for grave disability.

After he was treated with anti-psychosis drugs, the man calmed down enough to explain his AI-inspired dietary regime. This information, along with his test results, allowed the medical staff to diagnose him with bromism, a toxic accumulation of bromide. Bromide levels are typically less than around 10 mg/L in most healthy individuals; this patient's levels were measured at 1,700 mg/L. Bromism was a relatively common condition in the early 20th century, and is estimated to have once been responsible for up to 8 percent of psychiatric admissions. But cases of the condition drastically dropped in the 1970s and 1980s, after medications containing bromides began to be phased out.

Following diagnosis, the patient was treated over the course of three weeks and released with no major issues.

It is important to consider that ChatGPT and other AI systems can generate scientific inaccuracies, lack the ability to critically discuss results, and ultimately fuel the spread of misinformation.

https://www.acpjournals.org/doi/10.7326/aimcc.2024.1260

Comment by Dr. Krishna Kumari Challa on August 14, 2025 at 10:16am

Electrical implant approved for arthritis
A 2-centimetre implant that suppresses the symptoms of rheumatoid arthritis is the first electrical device approved to treat an autoimmune condition. The chip, called a Setpoint System, is implanted into a person’s neck and sends electrical pulses through the vagus nerve. In people with rheumatoid arthritis, these signals tell the immune system to stop attacking the joints. Similar implants are now in clinical trials for other autoimmune conditions, including lupus and inflammatory bowel disease.

https://www.smithsonianmag.com/smart-news/new-implanted-device-coul...

Comment by Dr. Krishna Kumari Challa on August 14, 2025 at 10:13am

Why some wounds heal without scars
Some parts of our bodies — such as the insides of the mouth and uterus — heal without scarring. Now researchers are delving into why this happens, and how it might help to head off some of the downsides of scars. The team compared mouth and face skin and found that, in mice, specialized skin cells communicate differently during healing: in mouth cells, a cell signaling pathway and a protein seem to prevent the formation of scars. Samples of human skin biopsies seem to back up the findings.

https://www.science.org/doi/10.1126/scitranslmed.adk2101?utm_source...

Comment by Dr. Krishna Kumari Challa on August 14, 2025 at 9:26am

Maternal microbes play a significant role in shaping early brain development, study suggests

Research finds that microbes play an important role in shaping early brain development, specifically in a key brain region that controls stress, social behaviour, and vital body functions.

The study, published in Hormones and Behavior, used a mouse model to highlight how natural microbial exposure not only impacts brain structure immediately after birth but may even begin influencing development while still in the womb. A mouse model was chosen because mice share significant biological and behavioural similarities with humans and there are no other alternatives to study the role of microbes on brain development. 

This work is of significance because modern obstetric practices, like peripartum antibiotic use and Cesarean delivery, disrupt maternal microbes.

At birth, a newborn body is colonized by microbes as it travels through the birth canal. Birth also coincides with important developmental events that shape the brain.

The research team focused on a brain region called the paraventricular nucleus of the hypothalamus (PVN), which plays a central role in regulating stress, blood pressure, water balance, and even social behavior. Their previous work had shown that mice raised without microbes, or germ-free mice, had more dying neurons in the PVN during early development. The new study set out to determine whether this increased cell death translated to changes in neuron number in the long run, and if any effects could be caused by the arrival of microbes at birth or if they began in the womb via signals from maternal microbes.

. The researchers used a cross-fostering approach. Germ-free newborn mice were placed with mothers that had microbes and compared them to control groups. When the brains of these mice were examined just three days after birth, the results were striking: All mice gestated by germ-free mothers had fewer neurons in the PVN, regardless of whether they received microbes after birth. The team also found that germ-free adult mice had fewer neurons in the PVN.

This study shows that microbes play an important role in sculpting a brain region that is paramount for body functions and social behavior. In addition, the study indicates that microbial effects start in the womb via signaling from maternal microbes.

Rather than shunning our microbes, we should recognize them as partners in early life development. They're helping build our brains from the very beginning, say the researchers

 Yvonne C. Milligan et al, The microbiota shapes the development of the mouse hypothalamic paraventricular nucleus, Hormones and Behavior (2025). DOI: 10.1016/j.yhbeh.2025.105742

Comment by Dr. Krishna Kumari Challa on August 14, 2025 at 9:16am

Researchers uncover surprising limit on human imagination

Human beings can juggle up to 10 balls at once. But how many can they move through the air with their imaginations?

The answer, published in Nature Communications, astonished even the researchers pursuing the question. The cognitive psychologists found people could easily imagine the trajectory of a single ball after it disappeared. But the imagination couldn't simultaneously keep tabs on two moving balls that fell from view.

The researchers set out to test the capacity limits of the imagination, and they found that it was just one!

Halely Balaban et al, The capacity limits of moving objects in the imagination, Nature Communications (2025). DOI: 10.1038/s41467-025-61021-8

Comment by Dr. Krishna Kumari Challa on August 14, 2025 at 9:07am

In-mouth hydrogel releases artificial saliva to treat dry mouth

Saliva is more than spit. It helps with chewing and swallowing, protects teeth and gums, and even has antimicrobial and digestive properties. However, certain conditions or medical treatments, such as hemodialysis, chemotherapy and radiation therapy, reduce natural saliva production. Now, researchers publishing in ACS Applied Polymer Materials have created a reusable hydrogel that releases artificial saliva over time, which could help provide sustained relief from dry mouth.

Dry mouth is a condition whereby the salivary glands do not produce enough saliva. Many medications to treat dry mouth boost natural saliva production, but they either provide temporary relief or have unwanted side effects, including mouth irritation and tooth erosion. Previous research identified that artificial saliva, often used in laboratory studies, could be a promising alternative to current medications.

Like natural saliva, artificial saliva is mostly water and contains mucins—a class of compounds that lubricate the mouth and have antimicrobial properties.

To create the reservoir, the researchers mixed artificial saliva with a biocompatible polymer poly(hydroxyethyl methacrylate), which is commonly used in medical applications such as contact lenses. The resulting hydrogel is a clear blob roughly the size of a U.S. quarter and small enough to fit in the inner cheek or below the tongue.

To determine how much artificial saliva a single reservoir could absorb, the researchers submerged it in artificial saliva for 6 hours. The saliva gel expanded up to 400% of its original volume, indicating that the gel has a high saliva storage capacity.

Next, the researchers tested the reservoir's ability to release stored saliva. The gel released all stored saliva over a 4-hour time span at 98.6 degrees Fahrenheit (37 degrees Celsius), starting off a little faster and then slowing over time. This demonstrates that human body temperature helps initiate saliva release from the hydrogel.

The researchers also report consistent saliva release rates across five consecutive tests with a single reservoir, demonstrating its potential as a reusable treatment option. Lastly, cultured cells in contact with the gel had no change to their survival or growth rates, indicating the reservoir's biocompatibility.

 Suman Debnath et al, Poly(hydroxyethyl methacrylate) Saliva-Gel: A Polymer-Based Solution for Xerostomia Treatment, ACS Applied Polymer Materials (2025). DOI: 10.1021/acsapm.5c00881

Comment by Dr. Krishna Kumari Challa on August 14, 2025 at 9:01am

Ultimately, HAR123 promotes a particularly advanced human trait called cognitive flexibility, or the ability to unlearn and replace previous knowledge.
In addition to providing new insights into the biology of the human brain, the results also offer a molecular explanation for some of the radical changes that have occurred in the human brain over the course of our evolution. This is supported, for example, by the authors' finding that the human version of HAR123 exerts different molecular and cellular effects than the chimpanzee version in both stem cells and neuron precursor cells in a petri dish.

 Kun Tan et al, An ancient enhancer rapidly evolving in the human lineage promotes neural development and cognitive flexibility, Science Advances (2025). DOI: 10.1126/sciadv.adt0534. www.science.org/doi/10.1126/sciadv.adt0534

Part 2

Comment by Dr. Krishna Kumari Challa on August 14, 2025 at 9:00am

A genetic twist that sets human brains apart

Research  has shed new light on an age-old question: what makes the human brain unique? The study is published online in Science Advances.

The  discovery comes from their investigation of human-accelerated regions (HARs)—sections of the human genome that have accumulated an unusually high level of mutations as humans have evolved. There is a lot of scientific interest in HARs, as they are hypothesized to play an essential role in conferring human-specific traits, and also have links to neurodevelopmental disorders, such as autism.

One reason why scientists think that HARs confer human-specific traits is they have undergone rapid changes in their genetic sequences since we split from our closest living relative—the chimpanzee—approximately 5 million years ago.

Now researchers have identified one particular HAR—called HAR123—that appears to be instrumental in shaping the human brain. The researchers found that HAR123 itself is not a gene, but is instead a type of molecular "volume control" known as a transcriptional enhancer. Transcriptional enhancers control which genes are activated, how much they are activated, and at what times they are activated during an organism's development.

Through its role as a transcriptional enhancer, HAR123 promotes the development of neural progenitor cells, the cells that give rise to the two main types of brain cells—neurons and glial cells. HAR123 also influences the ratio of neurons and glial cells that form from neural progenitor cells. 

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