Comment

Comment by Dr. Krishna Kumari Challa on September 27, 2024 at 9:46am

In the new study, mice (which have many genetic and physiological similarities to humans) developed a rodent form of psoriasis after being exposed to high levels of skin-produced hepcidin.

This over-abundance of the hormone caused the animals' skin cells to retain far more iron than was required. In turn, this excess iron triggered both a hyperproliferation of skin cells and an abnormally high concentration of inflammation-inducing neutrophils (a type of immune system cell) in the topmost layer of skin.

These two outcomes—an overproduction of skin cells and an abundance of neutrophils—are main features of human psoriasis.

Psoriasis runs in families, though experts believe "environmental" factors such as weight, infections and smoking are also triggers.

Currently there is no cure for psoriasis, though treatments that include topical creams, light therapy and oral drugs can help keep symptoms under control for patients with some forms of the condition. Recent treatments have focused on targeting the immune pathways that contribute to the development of psoriasis.

Elise Abboud et al, Skin hepcidin initiates psoriasiform skin inflammation via Fe-driven hyperproliferation and neutrophil recruitment, Nature Communications (2024). DOI: 10.1038/s41467-024-50993-8

Part 2

Comment by Dr. Krishna Kumari Challa on September 27, 2024 at 9:45am

A faulty iron hormone in the skin may be the root cause of psoriasis

Scientists may have uncovered the root cause of psoriasis, a chronic and sometimes debilitating skin disease that affects 2–3% of the global population. The condition is characterized by red, scaly patches that impact the quality of a patient's life and can sometimes be life-threatening.

New research strongly suggests the hormone hepcidin may trigger the onset of the condition. This marks the first time hepcidin has been considered a potential causal factor. In mammals, hepcidin is responsible for regulating iron levels in the body.

The study is published in the journal Nature Communications.

The researchers hope their finding will lead to the development of new drugs able to block the action of the hormone.

Those most likely to benefit from such a treatment are patients with pustular psoriasis (PP)—a particularly severe and treatment-resistant form of the disease that can affect a patient's nails and joints as well as skin.

Psoriasis is a life-changing dermatological disease. Patients face a potentially disfiguring and lifelong affliction that profoundly affects their lives, causing them both physical discomfort and emotional distress. The condition can also lead to other serious health conditions.

A new treatment targeting iron hormone imbalance in the skin offers hope. This innovative approach could significantly enhance the quality of life for millions, restoring their confidence and well-being.

Iron is an essential trace metal, not just for transporting oxygen through the body's circulatory system but also for maintaining healthy skin. It's involved in many essential cellular functions, including wound healing, collagen production and immune function. However, iron overload in the skin can be harmful, amplifying the damaging effects of UV sunlight and causing hyperproliferative chronic diseases (where cells grow and multiply more than normal), including psoriasis.

Studies going back 50 years have reported high iron concentrations in the skin cells of psoriatic patients. However, the cause of this excess and its significance to the condition have remained unclear until now.

The new study is the first to name hepcidin as the likely link.

Hepcidin is responsible for controlling how much iron is absorbed from food and later released into the body. In healthy individuals, it's produced exclusively in the liver. However, the new study has found that in people with psoriasis, the hormone is also generated in the skin.

Part 1

Comment by Dr. Krishna Kumari Challa on September 27, 2024 at 9:36am

Scientists discover 'pause button' in human development

Researchers have discovered a potential "pause button" in the earliest stages of human development.

Whether humans can control the timing of their development has long been debated. The new study suggests that this "pause button" can be activated in human cells as well. The findings have significant implications for our understanding of early human life and may improve reproductive technologies.

In some mammals, the timing of the normally continuous embryonic development can be altered to improve the chances of survival for both the embryo and the mother. This mechanism to temporarily slow development, called embryonic diapause, often happens at the blastocyst stage, just before the embryo implants in the uterus.

During diapause, the embryo remains free-floating and pregnancy is extended. This dormant state can be maintained for weeks or months before development is resumed, when conditions are favorable. Although not all mammals use this reproductive strategy, the ability to pause development can be triggered experimentally. Whether human cells can respond to diapause triggers remained an open question.

Now a study has identified that the molecular mechanisms that control embryonic diapause also seem to be actionable in human cells.

In their research, the scientists did not carry out experiments on human embryos and instead used human stem cells and stem cell-based blastocyst models called blastoids. These blastoids are a scientific and ethical alternative to using embryos for research. The researchers discovered that modulation of a specific molecular cascade, the mTOR signaling pathway, in these stem cell models induces a dormant state remarkably akin to diapause.

When the researchers treated human stem cells and blastoids with an mTOR inhibitor they observed a developmental delay, which means that human cells can deploy the molecular machinery to elicit a diapause-like response.

This dormant state is characterized by reduced cell division, slower development and a decreased ability to attach to the uterine lining. Importantly, the capacity to enter this dormant stage seems to be restricted to a brief developmental period.

The developmental timing of blastoids can be stretched around the blastocyst stage, which is exactly the stage where diapause works in most mammals.  Moreover, this dormancy is reversible, and blastoids resume normal development when the mTOR pathway is reactivated.

The researchers  concluded that humans, like other mammals, might possess an inherent mechanism to temporarily slow down their development, even though this mechanism may not be used during pregnancy.

This potential may be a vestige of the evolutionary process that we no longer make use of," say the researchers. "Although we have lost the ability to naturally enter dormancy, these experiments suggest that we have nevertheless retained this inner ability and could eventually unleash it."

 mTOR activity paces human blastocyst stage developmental progression, Cell (2024). DOI: 10.1016/j.cell.2024.08.048. www.cell.com/cell/fulltext/S0092-8674(24)00977-2

Comment by Dr. Krishna Kumari Challa on September 27, 2024 at 9:15am

When the National Institute for Medical Research (NIMR) merged with the Crick in 2015, mouse embryos were transferred from the former building to the latter, and this included the mice with Sox3 mutations.

When these mice reached the weaning stage at the Crick, the researchers were surprised to find that they no longer had the expected hormonal deficiencies.

After exploring a number of possible causes, researchers compared the microbiome – bacteria, fungi and viruses that live in the gut – in the mice from the Crick and mice from the NIMR, observing several differences in its makeup and diversity. This could have been due to the change in diet, water environment, or other factors that accompanied the relocation.

They also examined the number of NG2 glia in the Crick mice, finding that these were also at normal levels, suggesting that the Crick-fed microbiome was somehow protective against hypopituitarism.

To confirm this theory, the researchers transplanted fecal matter retained from NIMR mice into Crick mice, observing that the Crick mice once again showed symptoms of hypopituitarism and had lower numbers of NG2 glia.

Although the exact mechanism is unknown, the scientists conclude that the make-up of the gut microbiome is an example of an important environmental factor having a significant influence on the consequences of a genetic mutation, in this case influencing the function of the hypothalamus and pituitary gland.

Galichet, C. et al. Sox3-null hypopituitarism depends on median eminence NG2-glia and is influenced by aspirin and gut microbiota., PLoS Genetics (2024). DOI: 10.1371/journal.pgen.1011395

Part 2

Comment by Dr. Krishna Kumari Challa on September 27, 2024 at 9:13am

The gut microbiome can influence hormone levels, mouse study shows

Researchers at the Francis Crick Institute have shown that the balance of bacteria in the gut can influence symptoms of hypopituitarism in mice. They also showed that aspirin was able to improve hormone deficiency symptoms in mice with this condition.

People with mutations in a gene called Sox3 develop hypopituitarism, where the pituitary gland doesn't make enough hormones. It can result in growth problems, infertility and poor responses of the body to stress.

In research published recently in PLOS Genetics, the scientists at the Crick removed Sox3 from mice, causing them to develop hypopituitarism around the time of weaning (starting to eat solid food).

They found that mutations in Sox3 largely affect the hypothalamus in the brain, which instructs the pituitary gland to release hormones. However, the gene is normally active in several brain cell types, so the first task was to ask which specific cells were most affected by its absence.

The scientists observed a reduced number of cells called NG2 glia, suggesting that these play a critical role in inducing the pituitary gland cells to mature around weaning, which was not known previously. This could explain the associated impact on hormone production.

The team then treated the mice with a low dose of aspirin for 21 days. This caused the number of NG2 glia in the hypothalamus to increase and reversed the symptoms of hypopituitarism in the mice.

Although it's not yet clear how aspirin had this effect, the findings suggest that it could be explored as a potential treatment for people with Sox3 mutations or other situations where the NG2 glia are compromised.

Part 1

Comment by Dr. Krishna Kumari Challa on September 27, 2024 at 9:05am

Researchers discover treatment for major cause of recurrent pregnancy loss

Among women who experience recurrent pregnancy loss, around 20% test positive for a specific antibody that targets the mother's own body. A research team has now found a treatment that drastically increases these women's chances of carrying to full-term without complications.

They have published their results in the journal Frontiers in Immunology.

Recurrent pregnancy loss is a condition of women who have lost two or more pregnancies for non-obvious reasons.

The researchers enlisted the help of obstetricians across five hospitals in Japan and, over the course of two years, analyzed the blood of consenting women suffering from recurrent pregnancy loss for the antibodies. If any of these women got pregnant during this time frame, their doctors would offer treatment options also containing those drugs that are effective against the chemically similar condition, specifically, low-dose aspirin or a drug called "heparin." have previously found that in 20% of these women, they can detect a specific antibody in their blood that targets their own bodies. There is no known treatment for this particular condition till now , but the antibodies have a similar target to those that play a role in a different condition that has an established treatment.

The researchers enlisted the help of obstetricians across five hospitals in Japan and, over the course of two years, analyzed the blood of consenting women suffering from recurrent pregnancy loss for the antibodies. If any of these women got pregnant during this time frame, their doctors would offer treatment options also containing those drugs that are effective against the chemically similar condition, specifically, low-dose aspirin or a drug called "heparin." 

The research team then observed how many of the women who included these drugs in their treatment had full-term live births or pregnancy complications and compared that to the pregnancy outcomes in women who did not take either of the two drugs.

The researchers report that women who received the treatment were much more likely to have live births (87% did) compared to the ones without treatment (of which only 50% had live births). In addition, among the live births, the treatment reduced the likelihood of complications from 50% to 6%.

The sample size was rather small (39 women received the treatment and eight did not), but the results still clearly show that a treatment with low dose aspirin or heparin is very effective in preventing pregnancy loss or complications also in women who have these newly discovered self-targeting antibodies.

Many women who tested positive for the newly discovered self-targeting antibodies also tested positive for the previously known ones. However, the Kobe University-led team found that women who only had the newly discovered antibodies and who received the treatment were even more likely to have a live birth (93%) and, among these, none had pregnancy complications.

Low-dose aspirin and heparin treatment improves pregnancy outcome in recurrent pregnancy loss women with anti-β2-glycoprotein I/HLA-DR autoantibodies: A prospective, multicenter, observational study, Frontiers in Immunology (2024). DOI: 10.3389/fimmu.2024.1445852

Comment by Dr. Krishna Kumari Challa on September 26, 2024 at 10:17am

Medicinal tree successfully grown from 1,000-year-old seed found in cave

An international team of botanists, agriculturists and historians has successfully grown a mature tree from an ancient seed found in a cave in Israel. In their paper, published in the journal Communications Biology, the group describes where the seed was found, the work that was done to discover its origins and what they have learned about its history as it has sprouted and grown into a mature tree.

In the 1980s, researchers excavating a cave in the Judean Desert, in Israel, uncovered a seed that was subsequently dated to sometime between 993 and 1202 AD, making it approximately 1,000 years old. Testing of the seed suggested that it was still viable, so the research team planted and tended to it. A little while later, it sprouted. Now, 14 years later, the tree has grown to maturity.

The tree, which the team has named Sheba, is approximately 3 meters in height with green leaves on its limbs. As the tree has grown, the researchers have conducted a study of its wood, resin and leaves. They report that its type is now extinct.
They also found evidence of pentacyclic triterpenoids—compounds that are known to reduce inflammation in human patients. And they found an oil type, a squalene that is known to be an antioxidant and which has also been used as a skin treatment.

Finding the seed in a cave, the team notes, suggests that people living in the region planted such trees, further suggesting they knew of its medicinal qualities. This, they theorize, may be evidence that resin from the tree might be the "tsori" medicinal compound mentioned in the Bible several times.

Sarah Sallon et al, Characterization and analysis of a Commiphora species germinated from an ancient seed suggests a possible connection to a species mentioned in the Bible, Communications Biology (2024). DOI: 10.1038/s42003-024-06721-5

Comment by Dr. Krishna Kumari Challa on September 26, 2024 at 9:24am

Preclinical studies suggest a drug-free nasal spray could ward off respiratory infections

A new study details how a nasal spray formulated by investigators may work to protect against viral and bacterial respiratory infections. Based on their preclinical studies, the researchers say the broad-spectrum nasal spray is long-lasting, safe, and, if validated in humans, could play a key role in reducing respiratory diseases and safeguarding public health against new threats.

The COVID pandemic showed us what respiratory pathogens can do to humanity in a very short time. That threat hasn't gone away. 

Influenza and COVID-19 infections cause thousands of deaths and hundreds of thousands of cases of severe disease every year. Milder infections cause significant discomfort, resulting in missed work or school.

Vaccines against these viruses can be beneficial, but they're not accepted by some.

 Masks are also helpful but aren't perfect, either—they can leak, and many people wear them improperly or choose not to wear them at all.

So we need new, additional ways to protect ourselves and reduce the transmission of the disease.

Most viruses enter our system through the nose. When we catch an airborne infection like the flu and COVID, we breathe out tiny droplets of fluids that contain the pathogen. Healthy people around us breathe in these pathogen-containing droplets, which attach inside their nose and infect the cells that line the nasal passageways.

The pathogen replicates and can be released back into the air when an individual who is sick, whether they know it or not, sneezes, coughs, laughs, sings, or even just breathes.

The new study details the research team's efforts to create a nasal spray to defend against airborne respiratory illness.

The spray, called Pathogen Capture and Neutralizing Spray (PCANS) in the paper, was developed using ingredients from the FDA's Inactive Ingredient Database (IID), which have been previously used in approved nasal sprays, or from the Generally Recognized as Safe (GRAS) list of the FDA

The researchers developed a drug-free formulation using these compounds to block germs in three ways—PCANS forms a gel-like matrix that traps respiratory droplets, immobilizes the germs, and effectively neutralizes them, preventing infection.

The researchers developed the formulation and studied its ability to capture respiratory droplets in a 3D-printed replica of a human nose. They showed that when sprayed in the nasal cavity replica, PCANS captured twice as many droplets as mucus alone.

PCANS forms a gel, increasing its mechanical strength by a hundred times, forming a solid barrier.

It blocked and neutralized almost 100% of all viruses and bacteria the researchers tested, including Influenza, SARS-CoV-2, RSV, adenovirus, K Pneumonia and more.

Experiments in mice showed that a single dose of the PCANS nasal spray could effectively block infection from an influenza virus (PR8) at 25 times the lethal dose. Virus levels in the lungs were reduced by >99.99%, and the inflammatory cells and cytokines in the lungs of PCANS-treated animals were normal. "The formulation's ability to inactivate a broad spectrum of pathogens, including the deadly PR8 influenza virus, demonstrates its high effectiveness.

Joseph, J et al. Toward a Radically Simple Multi-Modal Nasal Spray for Preventing Respiratory Infections, Advanced Materials (2024). DOI: 10.1002/adma.202406348

Comment by Dr. Krishna Kumari Challa on September 26, 2024 at 9:10am

How do rare genetic variants affect health? AI provides more accurate predictions

Whether we are predisposed to particular diseases depends to a large extent on the countless variants in our genome. However, particularly in the case of genetic variants that only rarely occur in the population, the influence on the presentation of certain pathological traits has so far been difficult to determine.

Researchers  have introduced an algorithm based on deep learning that can predict the effects of rare genetic variants.

The paper, "Integration of Variant annotations using deep set networks boosts rare variant testing," has been published in Nature Medicine .

The method allows persons with high risk of disease to be distinguished more precisely and facilitates the identification of genes that are involved in the development of diseases.

Every person's genome differs from that of their fellow human beings in millions of individual building blocks. These differences in the genome are known as variants. Many of these variants are associated with particular biological traits and diseases. Such correlations are usually determined using so-called genome-wide association studies.

But the influence of rare variants, which occur with a frequency of only 0.1% or less in the population, is often statistically overlooked in association studies.

Rare variants in particular often have a significantly greater influence on the presentation of a biological trait or a disease.

AI  can therefore help to identify those genes that play a role in the development of a disease and that can then point us in the direction of new therapeutic approaches.

More details can be found here:  Integration of Variant annotations using deep set networks boosts rare variant testing, Nature Medicine (2024). DOI: 10.1038/s41588-024-01919-z. www.nature.com/articles/s41588-024-01919-z

Comment by Dr. Krishna Kumari Challa on September 26, 2024 at 8:53am

'Invisible forest' of phytoplankton thrives as ocean warms, study shows

An "invisible forest" of phytoplankton is thriving in part of our warming ocean, new research shows.

Phytoplankton are tiny drifting organisms that do about half of the planet's primary production (forming living cells by photosynthesis). The new study examined phytoplankton at the ocean surface and the subsurface—a distinct layer of water beneath—to see how climate variability is affecting them.

 The findings show these two communities are reacting differently. The paper is titled "Climate variability shifts the vertical structure of phytoplankton in the Sargasso Sea."

Over the last decade, the total biomass (living material) of subsurface phytoplankton has increased in response to warming.

Meanwhile, surface phytoplankton now has less chlorophyll—making it less green—but in fact, total biomass has remained stable.

Based on 33 years of data from the Bermuda Atlantic Time-series Study (BATS) in the Sargasso Sea, the findings also suggest the depth of the surface mixed-layer (region of turbulence at the surface of the ocean) has shallowed as the ocean rapidly warmed in the last decade.

It's important to understand these trends because phytoplankton are the foundation of the marine food web, and play a key role in removing carbon dioxide from the atmosphere.

These findings reveal that deep-living phytoplankton, which thrive in low-light conditions, respond differently to ocean warming and climate variability compared to surface phytoplankton.

We typically rely on satellite observations to monitor phytoplankton, but the subsurface is hidden from satellite view.  But this study highlights the limitations of satellite observations, and underscores the urgent need for improved global monitoring of phytoplankton below what satellites can see. 

Climate variability shifts the vertical structure of phytoplankton in the Sargasso Sea, Nature Climate Change (2024).

• ‹ Previous
• 1
• …
• 109
• 110
• 111
• 112
• 113
• …
• 1053
• Next ›
• Page