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Comment by Dr. Krishna Kumari Challa on January 22, 2025 at 11:40am

New effective treatment for deadly pancreatic cancer may be on its way

Pancreatic cancer is one of the deadliest of all cancers. Only 12% of men diagnosed with pancreatic cancer are alive five years after diagnosis; for women it is 14%.

In pancreatic cancer, symptoms are unclear and often emerge late in its progression. It is difficult to treat once the cancer has spread, as it cannot be removed completely with surgery.

Now researchers  have made significant advances in developing a treatment for pancreatic cancer and a new study published in Science Advances depicts how it is done. The study is based on the ADC (antibody drug conjugates) technique, which is being used to treat other types of cancers.

This study shows promising results with a new type of drug that can fight the cancer on several fronts. The treatment directly kills the cancer cells and the support cells that the cancer uses to grow and shield itself.

By targeting the support cells, the treatment also releases toxins that can kill neighboring cancer cells. Additionally, destroying the support cells weakens the tumor structure, making it easier for the body's immune system to attack and eliminate it.

The ADC consists of three main components: an antibody, a chemical linker that ties the antibody to the drug, and a strong chemotherapeutic drug. Once the ADC has located and entered the cancer cell, the linker decomposes, activating the chemotherapy and killing the cancer cell from the inside. This Trojan horse strategy offers targeted treatment without affecting the healthy cells.

Because ADC treatment is extremely accurate and causes minimal damage to healthy cells, it is a likely candidate for treatment of the more difficult cancers.

As part of the process, the researchers have humanized the ADC antibody, which means that we have changed its structure to resemble antibodies naturally occurring in the human body. This adjustment ensures that the body's immune system does not recognize the antibody as foreign and attack it. Humanization is a critical step in making the treatment both safe and effective for patients and represents a key milestone on the path towards clinical trials.

The researchers are now working to further develop the drug and get it ready for clinical testing on humans with pancreatic cancer.

Virginia Metrangolo et al, Targeting uPAR with an antibody-drug conjugate suppresses tumor growth and reshapes the immune landscape in pancreatic cancer models, Science Advances (2025). DOI: 10.1126/sciadv.adq0513

Comment by Dr. Krishna Kumari Challa on January 22, 2025 at 11:31am

Scientists finally know how cells build a structure that lets them migrate

Some of the body's cells stay put for life, while others are free to roam. To move, these migratory cells rely on filopodia—sensitive, finger-like protrusions that reach out from the cell membrane into the local environment. In a healthy cell, this can be a lifesaver: say, when an immune cell is speeding to the site of an infection. But filopodia can also wreak havoc: metastatic cancer cells use them to invade new regions of the body.

Filopodia are composed of hexagonal bundles of proteins that give them structure and strength. How these intricate bundles come together has been a puzzle for more than 40 years. A major piece of that puzzle has now been solved by Rockefeller University's Laboratory of Structural Biophysics and Mechanobiology, which developed advanced imaging technology to reveal how underlying proteins build these cohesive assemblies.

The findings, published in Nature Structural & Molecular Biology, may improve some cancer treatments already in development, as understanding the structure of filopodia and the changes they undergo may help to refine these therapies or inspire new ones.

The study marks the first time such a complex higher-order protein assembly has been imaged at the atomic level—a technological advance that other scientists can now use to study similarly complex configurations.

 Rui Gong et al, Fascin structural plasticity mediates flexible actin bundle construction, Nature Structural & Molecular Biology (2025). DOI: 10.1038/s41594-024-01477-2

Comment by Dr. Krishna Kumari Challa on January 22, 2025 at 11:25am

Discovery shows oyster blood proteins improve antibiotic effectiveness

While slurping oysters is not likely to replace popping a pill, they could help in the fight against superbugs. A groundbreaking find by researchers has shown oysters might be able to help treat a growing worldwide public health problem: antibiotic-resistant bacteria.

In a study published in PLOS ONE, the researchers demonstrate a protein in the blood, or hemolymph, of a Sydney Rock Oyster not only kills bacteria but increases the effectiveness of some conventional antibiotics against a range of clinically important bacteria.

This new research supports the potential use of natural products from oysters to treat bacterial infections. Importantly, the oyster hemolymph proteins were not toxic to human lung cells, suggesting it should be possible to optimize a safe, effective dose. 

 Antimicrobial proteins from oyster hemolymph improve the efficacy of conventional antibiotics, PLOS ONE (2025). DOI: 10.1371/journal.pone.0312305. journals.plos.org/plosone/arti … journal.pone.0312305

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Comment by Dr. Krishna Kumari Challa on January 22, 2025 at 11:15am

Scientists create world's first fully-3D printed microscope in under three hours

Scientists  have created the world's first fully 3D printed microscope in under three hours and for less than £50—a fraction of the cost of traditional devices.

Using a publicly available design from the website OpenFlexure the scientists produced the microscope's frame—and clear plastic lenses they designed themselves—using low-cost, accessible 3D printers.

The microscope was completed by adding a shop-bought camera and a light, with the whole device controlled by a Raspberry Pi computer processor.

The researchers have presented their results in a paper submitted for publication in the Journal of Microscopy which is currently in pre-print on the server bioRxiv ahead of publication following peer review.

To test the imaging performance of the system, the scientists used standard test samples: a stained blood smear and a stained, thin section of mouse kidney. The microscope demonstrated sub-cellular resolution, clearly imaging individual red blood cells and detailed structures in the kidney sample.

This opens the doors to democratized access, rapid prototyping, and bespoke design of microscopes and optics at a fraction of the price of traditional microscopes. It could help scientists and medics in low-income countries around the world, as well as enabling students to learn more about science through accessible, cheap kit.

Jay Christopher et al, A fully 3D-printed optical microscope for low-cost histological imaging, bioRxiv (2024). DOI: 10.1101/2024.12.16.628684

Comment by Dr. Krishna Kumari Challa on January 22, 2025 at 10:41am

Biotin may shield brain from manganese-induced damage, study finds

While manganese is an essential mineral involved in many bodily functions, both deficiency and excessive exposure can cause health issues. Maintaining a balanced diet typically provides sufficient manganese for most individuals; however, high levels of exposure can be toxic, particularly to the central nervous system.

Chronic manganese exposure may result in a condition known as manganism, characterized by symptoms resembling Parkinson's disease, including tremors, muscle stiffness, and cognitive disturbances.

New research published in Science Signaling employs model systems and human nerve cells to show the mechanisms by which manganese inflicts damage to the central nervous system. The study also suggests that the vitamin biotin may have a protective effect, potentially mitigating manganese-induced damage.

Exposure to neurotoxic metals like manganese has been linked to the development of Parkinsonism. In this study, researchers applied untargeted metabolomics using high-resolution mass spectrometry and advanced cheminformatics computing in a newly developed model of parkinsonism, leading them to the discovery of biotin metabolism as a modifier in manganese-induced neurodegeneration.

Chronic occupational and environmental exposure to manganese, commonly from welding fumes and some sources of rural drinking water, increases the risk of Parkinsonian syndrome, which involves similar but distinct neurological symptoms of Parkinson's disease. Manganese has been previously shown to bind with the protein alpha-synuclein, causing it to misfold and accumulate in the brain.

Using the fruit fly Drosophila, researchers developed a model that mimics occupational manganese exposure in humans and found that manganese induced motor deficits, mitochondrial and lysosomal dysfunction, neuronal loss, and reduced lifespan in flies.

The team validated these findings using human dopaminergic neurons derived from induced pluripotent stem cells (iPSC) and demonstrated that manganese exposure selectively damages these cells. The loss of dopamine-producing cells is a hallmark of Parkinson's disease and Parkinsonian syndrome.

The research indicates that B vitamin biotin, a micronutrient synthesized by gut bacteria, enhances dopamine production in the brain. Biotin supplementation reversed neurotoxicity in flies and iPSC-derived neurons, improving mitochondrial function and reducing cell loss.

This finding aligns with a growing scientific recognition that Parkinson's is a multisystem disorder, with early symptoms often emerging in the gut, and that changes in the gut microbiome may contribute to the disease.

"Biotin supplementation shows potential as a therapeutic strategy to mitigate manganese-induced neurodegeneration, and the safety and tolerability of biotin in humans make it a promising candidate for further exploration," say the researchers.

Biotin-rich prebiotics or biotin-producing probiotics could provide non-pharmacological intervention options.

Biotin rescues manganese-induced Parkinson's disease phenotypes and neurotoxicity, Science Signaling (2025). DOI: 10.1126/scisignal.adn9868

Comment by Dr. Krishna Kumari Challa on January 22, 2025 at 10:19am

Further experiments on mice revealed that shortly after conception, more methyl groups appear on histones near certain genes in uterine fibroblasts. In response, these genes remain inactive, which enables the uterus to support pregnancy.

Over the course of pregnancy, levels of methylation on these histones fade in a slow and steady way, eventually reaching low enough levels that the nearby genes—related to pregnancy events like labor—are activated. This erosion, which does not require KDM6B, functions as a timer.

Essentially, what appears to happen is this timer gets wound up right at the beginning of pregnancy, and then progressively winds down. When histone methylation erodes enough, nearby genes flip on.

When the researchers blocked KDM6B, histones near certain genes accumulated too much methylation early in pregnancy. This increased "setpoint" meant that, despite erosion, these genes were not activated on time, delaying labour.
While the new study did not directly study preterm births, the newly discovered molecular timer could help control pregnancy length in humans.

If the newly studied molecular signals are disrupted in humans, they could be linked to preterm birth risk, his team hypothesizes. For instance, some women could begin pregnancy with lower than usual levels of histone methylation; and this could lead to the erosion of the methylation to turn on labor-related genes too quickly.

 KDM6B-dependent epigenetic programming of uterine fibroblasts in early pregnancy regulates parturition timing in mice, Cell (2025). DOI: 10.1016/j.cell.2024.12.019. www.cell.com/cell/fulltext/S0092-8674(24)01432-6

Part 2

Comment by Dr. Krishna Kumari Challa on January 22, 2025 at 10:17am

What's behind preterm birth? Scientists discover a molecular timer

A typical human pregnancy lasts 40 weeks, but most parents know this number is only a rough estimate. Babies are born on a seemingly unpredictable timeline, with a normal pregnancy ranging from 38 to 42 weeks. And 10% of all births are preterm, meaning they occur before 37 weeks of gestation, which puts babies at risk of a host of complications.

Now  researchers have discovered a molecular timer in mice that plays a role in controlling when they give birth. Surprisingly, the timer is activated in the very first days of pregnancy and operates within the uterus.

If the same set of molecules is found to be important in human pregnancies, it could lead to new tests to identify women who are at risk of preterm labour, as well as interventions to delay it.

DNA packaging during pregnancy

Throughout pregnancy, the female body undergoes massive biological shifts, with the activity of hundreds of genes going up or down within the uterus.

Researchers were studying a protein called KDM6B which regulates gene activity. They suspected that during pregnancy, KDM6B could help regulate the genes involved in the transition to labor.

KDM6B works by removing methyl chemical groups from histones—structures that help organize and package DNA within cells. In response to KDM6B, DNA becomes more accessible to other factors that regulate gene expression, turning on the activity of nearby genes.

The team noticed that when they blocked KDM6B, pregnancies in the mice became longer, and their babies were born later than usual.

At first, the scientists suspected that, late in pregnancy, KDM6B must be activating genes in the uterus's epithelial cells, which produce hormones known to trigger labor.

But when they carried out detailed analyses on different cell types, they found that KDM6B's effects on pregnancy length were tied to a different cell type called fibroblasts. These structural cells are not typically considered to play a role in the regulation of labor. Moreover, KDM6B regulated these fibroblasts during the first days of pregnancy.

These findings highlight a surprising role for uterine fibroblasts in regulating birth timing.

Part 1

Comment by Dr. Krishna Kumari Challa on January 22, 2025 at 9:55am

To answer this fundamental question, researchers analyzed data from 9,331 patients cataloged in the Cancer Genome Atlas and the Pan-Cancer Analysis of Whole Genomes. By comparing genetic mutations to epigenetic modifications, they found that mutations were predictably correlated with changes in DNA methylation, one type of epigenetic modification.
They found that a single mutation could cause a cascade of epigenetic changes across the genome, not just where the mutation occurred. Using this relationship, the researchers were able to make similar predictions of age using either mutations or epigenetic changes.

Epigenetic clocks have been around for years, but scientists are only now beginning to answer the question of why epigenetic clocks tick in the first place.

This study demonstrates for the first time that epigenetic changes are intricately and predictably tied to random genetic mutations.
The study's authors note that further research is needed to fully understand the relationship between somatic mutations and epigenetic changes in aging. However, the study's findings provide a major breakthrough in our understanding of the aging process and have important implications for the development of new therapies aimed at preventing or reversing aging.
If somatic mutations are the fundamental driver of aging and epigenetic changes simply track this process, it's going to be a lot harder to reverse aging than we previously thought, say the authors of this study.
This shifts our focus from viewing aging as a programmed process to one that's largely influenced by random, cumulative changes over time.

Zane Koch et al, Somatic mutation as an explanation for epigenetic aging, Nature Aging (2025). DOI: 10.1038/s43587-024-00794-x

Part 2

Comment by Dr. Krishna Kumari Challa on January 22, 2025 at 9:51am

Why our biological clock ticks: Research reconciles major theories of aging

Researchers have published results that shed new light on an old question: what causes aging at the molecular level? Their findings, published in Nature Aging, describe a never-before-seen link between the two most accepted explanations: random genetic mutations and predictable epigenetic modifications. The latter, also known as the epigenetic clock theory, has been widely used by scientists as a consistent, quantitative measure of biological aging.

The new research suggests that the process may not be so simple.

Major research institutions and companies are betting on turning back the epigenetic clock as a strategy to reverse the effects of aging, but this new research suggests that this may only be treating a symptom of aging, not the underlying cause.

If mutations are in fact responsible for the observed epigenetic changes, this fact could fundamentally change the way we approach anti-aging efforts in the future.

There are two prevailing theories about the relationship between aging and DNA. The somatic mutation theory suggests that aging is caused by the accumulation of mutations, permanent changes in our DNA sequence that occur randomly. The epigenetic clock theory suggests that aging occurs due to the accumulation of epigenetic modifications, minor changes to the chemical structure of DNA that do not alter the underlying sequence, but instead change which genes are on or off. Unlike mutations, epigenetic modifications can also be reversed in some cases.

Because epigenetic modifications only occur at specific sites on our genome rather than at random locations, they are easier to quantify and have become a go-to way for scientists to determine the "biological age" of cells. However, scientists have long wondered about the source of these epigenetic changes.

Part 1

Comment by Dr. Krishna Kumari Challa on January 22, 2025 at 9:15am

Neuronal subtypes study uncovers parallel gut-to-brain pathways that regulate feeding behaviours

The ability to regulate one's own food intake is essential to the survival of both humans and other animals. This innate ability ensures that the body receives the nutrients it needs to perform daily activities, without significantly exceeding calorie intake, which could lead to health problems and metabolic disorders.

Past neuroscience studies suggest that the regulation of food intake is supported by specific regions in the brain, including the hypothalamus and caudal nucleus of the solitary tract (cNTS), which is part of the brainstem. This key region in the brainstem is known to integrate sensory signals originating from the gut and then transform them into adaptive feeding behaviours.

While previous research has highlighted the key role of the cNTS in food intake regulation, the unique contribution of the different neuron subtypes within this brainstem region and the mechanisms by which they regulate feeding remain poorly understood. Better understanding these neuron-specific mechanisms could help to devise more effective therapeutic interventions for obesity and eating disorders.

Researchers recently carried out a study aimed at identifying neuronal subtypes in the mouse cNTS that are involved in how mice control their feeding behaviors. Their findings, published in Nature Neuroscience, show that different types of cNTS neurons process gut-originating signals via distinct sensory pathways, collectively contributing to the regulation of feeding.

The cNTS in the brainstem serves as a hub for integrating interoceptive cues from diverse sensory pathways. Understanding  the mechanisms by which cNTS neurons transform these signals into behaviours is vital too.

So the researchers systematically analyzed the brains and feeding behaviors of mice that were genetically intervened upon to turn "off" and "on" nine types of neurons in the cNTS. The researchers found that two key neuron populations, namely Th⁺ (tyrosine hydroxylase-expressing) and Gcg⁺ (glucagon-like peptide 1-expressing) neurons encoded different aspects of food intake.

Th⁺ cNTS neurons encode esophageal mechanical distension and transient gulp size via vagal afferent inputs, providing quick feedback regulation of ingestion speed.

By contrast, Gcg+ cNTS neurons monitor intestinal nutrients and cumulative ingested calories and have long-term effects on food satiation and preference. These nutritive signals are conveyed through a portal vein–spinal ascending pathway rather than vagal sensory neurons.

New studies could explore the unique contribution of the two broad neuron populations outlined by the researchers (i.e., Th⁺ and Gcg⁺ neurons), as well as their interactions with other brain regions in regulating feeding behaviours.

Hongyun Wang et al, Parallel gut-to-brain pathways orchestrate feeding behaviors, Nature Neuroscience (2024). DOI: 10.1038/s41593-024-01828-8

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