Publisher Health

Researchers at Queen’s University Belfast have revealed how the pathway of an identified protein could lead to early diagnosis and targeted treatment for several cancers and brain disorders.
The team of researchers discovered how the journey or molecular pathway of an identified protein is both essential for brain development and how an alteration to its pathway could result in the spread of cancer.
The study, published today in Nature Cell Biology, has revealed the molecular mechanisms of a timely and spatially controlled movement of cells that is essential for the migration of newborn neurons during brain development and can also cause the spread of cancer, or cancer metastasis throughout the body.
It is expected this discovery will have a huge impact on the fundamental understanding of cancer metastasis and brain development and could lead to earlier diagnosis and better treatments, the research authors said.
During brain development, neural stem cells give birth to neurons, which then migrate to specific locations within the brain where they form connections and mature in function. A defect in this process is known to cause several neurodevelopmental disorders. A better understanding of these events is key to decoding fundamental mechanisms of brain development and revealing novel diagnostics and therapeutic avenues for such disorders.
Cancer is a leading cause of death worldwide, accounting for nearly 10 million deaths in 2020, or nearly one in six deaths. The majority of tumours are solid, except for a few cancer types of blood origin. Often by the time solid tumours are detected, some cells from the primary tumor have begun to spread to other parts of the body by a process called metastasis, giving rise to secondary tumors whose cells are often resistant to chemotherapy. While surgical removal, chemotherapy and other types of anti-tumour therapy can target the primary tumour, metastasis makes the outcome unpredictable and can lead to more aggressive relapse. It is crucial to understand the features of cancer in order to tackle it.
Epithelial to Mesenchymal Transition (EMT) is a particular molecular pathway that enables cell migration and is vital for early development processes including brain development as well as for wound healing later in life but is also used by cancer cells for metastasis. The research team identified a particular protein, ZNF827, which they identified as a critical regulator of EMT. The study shows how the journey or molecular pathway of the protein is both employed for migration of newborn neurons to proper places during brain development and also exploited by tumour cells to gain migration potential and thereby cause metastasize to different organs.
Lead Author, Dr Vijay Tiwari from the Wellcome-Wolfson Institute for Experimental Medicine at Queen’s University, said: “Our study not only sheds light on the development of one of the most important organs in our body — the brain — but it also shows how the same protein that is key for brain development can also be the cause or target for the spread of cancer in the body, a real Jekyll and Hyde protein.
“The process for migrating newborn neurons to proper places during brain development is the same process exploited by tumour cells to gain migration potential, causing the movement of cancer throughout the body, or cancer metastasis.
“By identifying key regulators of these pathways, we open new opportunities for a therapeutic intervention against cancer and a better understanding of neurodevelopmental disorders involving defects in brain development.”
The international team includes researchers from Queen’s University Belfast, Salk Institute for Biological Studies, Altos Labs, University of Montpellier, Karolinska Institutet, University Medical Center of the Johannes Gutenberg University Mainz and Translational Oncology at the University Medical Center of the Johannes Gutenberg University Mainz gGmbH (TRON gGmbH).
This study was supported by the Deutsche Forschungsgemeinschaft, Wilhelm Sander Stiftung and Innovation to Commercialisation of University Research programme.
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Amid longstanding debate on the effectiveness of the tuberculosis vaccine, a new study suggests that the vaccine is protective against TB in children under 5, but adolescents and adults in high-burden countries may need additional protection to maintain immunity beyond childhood.
The tuberculosis (TB) vaccine, bacille Calmette-Guérin (BCG), is one of the most widely administered vaccines across the globe. Nearly 100 years old, it is the only vaccine ever administered to treat TB, which afflicts more than 10 million people each year.
Despite the age and widespread use of the BCG vaccine, there is still considerable debate on its effectiveness in preventing TB, and how long immunity may last after it is administered in infancy. And as experts study and propose new TB vaccines to supplement the BCG vaccine, an important consideration is the age at which these new vaccines should be administered to high-risk populations.
Now, a new study led by a Boston University School of Public Health (BUSPH) researcher provides new insight and clarity on these issues.
Published in The Lancet Global Health, the study found that BCG vaccination at birth does provide significant protection against TB disease — but only among children under 5 years old. The vaccine provided no protection among adolescents or adults in this study.
These results suggest that protectiveness from the BCG vaccine may begin to wane as children get older and, thus, children over 10 years old and adults should receive a booster BCG vaccine — and eventually a new, supplemental vaccine, as the researchers note that the BCG booster may also have limited efficacy — for immunity against TB beyond childhood. Unfortunately, a BCG booster has limited efficacy, so new vaccines are needed.

Computers that think more like human brains are inching closer to mainstream adoption. But many unanswered questions remain. Among the most pressing, what types of materials can serve as the best building blocks to unlock the potential of this new style of computing.
For most traditional computing devices, silicon remains the gold standard. However, there is a movement to use more flexible, efficient and environmentally friendly materials for these brain-like devices.
In a new paper, researchers from The University of Texas at Austin developed synaptic transistors for brain-like computers using the thin, flexible material graphene. These transistors are similar to synapses in the brain, that connect neurons to each other.
“Computers that think like brains can do so much more than today’s devices,” said Jean Anne Incorvia, an assistant professor in the Cockrell School of Engineering’s Department of Electrical and Computer Engineer and the lead author on the paper published today in Nature Communications. “And by mimicking synapses, we can teach these devices to learn on the fly, without requiring huge training methods that take up so much power.”
A combination of graphene and nafion, a polymer membrane material, make up the backbone of the synaptic transistor. Together, these materials demonstrate key synaptic-like behaviors — most importantly, the ability for the pathways to strengthen over time as they are used more often, a type of neural muscle memory. In computing, this means that devices will be able to get better at tasks like recognizing and interpreting images over time and do it faster.
Another important finding is that these transistors are biocompatible, which means they can interact with living cells and tissue. That is key for potential applications in medical devices that come into contact with the human body. Most materials used for these early brain-like devices are toxic, so they would not be able to contact living cells in any way.

UT Southwestern researchers have identified a molecular pathway responsible for the spread of glioblastoma to surrounding tissue in the brain, as well as an existing drug that curbed tumor growth in animal models. The findings, published in Nature Cell Biology, have led to a clinical trial that could offer new hope to patients with glioblastoma, the most common form of brain cancer in adults that kills hundreds of thousands of people worldwide each year.
“Glioblastoma’s invasive property is perhaps its most formidable barrier to treatment,” said Amyn Habib, M.D., Associate Professor of Neurology, member of both the Harold C. Simmons Comprehensive Cancer Center and Peter O’Donnell Jr. Brain Institute at UTSW, and a staff physician at the Dallas VA Medical Center. “We have identified a pathway that can suppress this cellular invasion, which could offer a new way to increase survival.”
Despite decades of research, the prognosis for most patients with glioblastoma remains dismal, with a median survival after diagnosis of just 15-18 months. Part of the challenge in treating this cancer is its invasive nature: Glioblastoma tumors invade surrounding healthy brain tissue, sending tentacle-like extensions out from the primary tumor that are impossible to remove with surgery alone and difficult to reach with chemotherapy.
Researchers have long considered the epidermal growth factor receptor (EGFR), a protein that sits on the surface of cells, as a driver of this cancer, Dr. Habib explained. In nearly half of glioblastoma patients, the gene that codes for EGFR is amplified, causing glioblastoma cells to produce far more molecular signals spurred by this protein and causing tumor cells to proliferate. Consequently, Dr. Habib added, several clinical trials have focused on inhibiting EGFR — but each has failed to improve the prognosis for glioblastoma.
EGFR on glioblastoma cells can send these signals in two ways: either without prompting, a state known as constitutive signaling, or when stimulated with proteins called ligands. The differences between these two pathways have been considered inconsequential, Dr. Habib said. Thus, glioblastoma patients with amplified EGFR have been grouped together in clinical trials.
In the new study, Dr. Habib and colleagues in the Habib lab and elsewhere showed that when cells with amplified EGFR were stimulated with ligands, this receptor appeared to act as a tumor suppressor, preventing invasion into healthy tissue both in laboratory and animal models. Further experiments showed that a cytoskeletal protein called BIN3 appears to be responsible for inhibiting this invasion. When the researchers dosed animals with amplified EGFR glioblastoma tumors with an FDA-approved arthritis drug called tofacitinib that increases the amount of EGFR ligands and BIN3, tumors remained smaller and were less likely to invade healthy brain tissue. Additionally, these animals survived significantly longer than animals that didn’t receive this drug.
Dr. Habib noted that tofacitinib could offer a new way to extend life for patients with both amplified EGFR and a relatively high level of EGFR ligands, a strategy he and his colleagues will explore in a clinical trial launching in September. For patients without high ligand numbers, he added, strategies previously explored to inhibit EGFR could potentially extend survival.
“These approaches could offer new tools in our arsenal to fight glioblastoma,” Dr. Habib said.
This study was funded by grants from the Department of Veterans Affairs (VA) (2I01BX002559-08) and the National Institutes of Health (1R01CA244212-01A1 and 1R01NS119225-01A1). The VA has filed a patent on the use of tofacitinib in glioblastoma, listing Dr. Habib as the inventor.
The clinical trial will be conducted at the Simmons Cancer Center.
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Research led by Drs. Yuhai Zhao and Walter J Lukiw at the LSU Health New Orleans Neuroscience Center and the Departments of Cell Biology and Anatomy, Neurology and Ophthalmology, reports for the first time a pathway that begins in the gut and ends with a potent pro-inflammatory toxin in brain cells contributing to the development of Alzheimer’s disease (AD). They also report a simple way to prevent it. Results are published in Frontiers in Neurology, available here.
The researchers found evidence that a molecule containing a very potent microbial-generated neurotoxin (lipopolysaccharide or LPS) derived from the Gram-negative bacteria Bacteroides fragilis in the human gastrointestinal (GI) tract generates a neurotoxin known as BF-LPS.
“LPSs in general are probably the most potent microbial-derived pro-inflammatory neurotoxic glycolipids known,” says Dr. Lukiw. “Many laboratories, including our own, have detected different forms of LPS within neurons of the Alzheimer’s disease-affected human brain.”
In this study, the researchers detail the pathway of BF-LPS from the gut to the brain and its mechanisms of action once there. BF-LPS leaks out of the GI tract, crosses the blood brain barrier via the circulatory system, and accesses brain compartments. Then it increases inflammation in brain cells and inhibits neuron-specific neurofilament light (NF-L,) a protein that supports cell integrity. A deficit of this protein leads to progressive neuronal cell atrophy, and ultimately cell death, as is observed in AD-affected neurons. They also report that adequate intake of dietary fiber can head off the process.
The novel features of this newly described pathological pathway are threefold. The AD-stimulating pathway begins inside of us — in our GI-tract microbiome — and therefore is very “locally sourced” and active throughout our lives. The highly potent neurotoxin BF-LPS is a natural by-product of GI-tract-based microbial metabolism. Bacteroides fragilis abundance in the microbiome, which is the source of the neurotoxin BF-LPS, can be regulated by dietary fiber intake.
“Put another way, dietary-based approaches to balance the microorganisms in the microbiome may be an attractive means to modify the abundance, speciation, and complexity of enterotoxigenic forms of AD-relevant microbes and their potential for the pathological discharge of highly neurotoxic microbial-derived secretions that include BF-LPS and other forms of LPS,” Lukiw explains.
The researchers conclude that an improved understanding of the interaction between the GI tract-Central Nervous System axis and the GI-tract microbiome and Alzheimer’s disease has considerable potential to lead to new diagnostic and therapeutic strategies in the clinical management of Alzheimer’s disease and other lethal, progressive, and age-related neurodegenerative disorders.
It has been estimated that Americans eat 10-15 grams of fiber a day on average. The USDA recommends that women up to age 50 consume 25 grams a day and men 38 grams. Over age 50, women and men should consume 21 and 30 grams daily, respectively.
According to the National Institutes of Health, Alzheimer’s disease is the most common diagnosis for patients with dementia and the sixth leading cause of death for Americans. Experts estimate that as many as 5.8 million Americans 65 and older have Alzheimer’s disease, and the prevalence in the United States is projected to increase to 13.8million by 2050.
LSU Health New Orleans co-authors included Drs. Vivian Jaber and Nathan Sharfman. Aileen Pogue from Alchem Biotech Research in Toronto Canada was also a co-author.
The research was supported by funding from LSU Health New Orleans, the Brown Foundation, the Joe and Dorothy Dorsett Innovation in Science Health Aging Award, and the National Institutes on Aging of the National Institutes of Health.

A possible way to tackle one of the underlying causes of asthma has been developed by researchers from Aston University and Imperial College London.
In tests in mice, the researchers were able to virtually eliminate asthmatic symptoms within two weeks and return their airways to near normal.
Just under 5.5 million people in the UK receive treatment for asthma and around 1,200 people die of the disease each year.
Asthma causes the airways to become thickened and constricted, resulting in symptoms such as wheezing and shortness of breath.
Current treatments, including steroids, provide short term relief from these symptoms, by either relaxing the airways or reducing inflammation. However, no current drugs address the structural changes asthma makes to the airway and lungs, in order to offer a longer-lasting treatment.
Lead researcher, Dr Jill Johnson, from Aston University’s School of Biosciences, said: “By targeting the changes in the airway directly, we hope this approach could eventually offer a more permanent and effective treatment than those already available, particularly for severe asthmatics who don’t respond to steroids. However, our work is still at an early stage and further research is needed before we can begin to test this in people.”
The research focused on a type of stem cell known as a pericyte, which is mainly found in the lining of blood vessels. When asthmatics have an allergic and inflammatory reaction, for example to house dust mites, this causes the pericytes to move to the airway walls. Once there, the pericytes develop into muscle cells and other cells that make the airway thicker and less flexible.
This movement of the pericytes is triggered by a protein known as CXCL12. The researchers used a molecule called LIT-927 to block the signal from this protein, by introducing it into the mice’s nasal passages. Asthmatic mice that were treated with LIT-927 had a reduction in symptoms within one week and their symptoms virtually disappeared within two weeks. The researchers also found that the airway walls in mice treated with LIT-927 were much thinner than those in untreated mice, closer to those of healthy controls.
The team are now applying for further funding to carry out more research into dosage and timing, This would help them to determine when might be the most effective time to administer the treatment during the progress of the disease, how much of LIT-927 is needed, and to better understand its impact on lung function. They believe that, should this research be successful, it will still be several years before the treatment could be tested in people.
The research was funded by the Medical Research Council, part of UK Research and Innovation and is published in Respiratory Medicine.
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In the pursuit of accurate diagnoses for illnesses, doctors have traditionally used multiple methods — including culturing patient samples on a wide variety of media, reviewing countless medical records and analyzing clinical data using complex mathematical algorithms — to try to identify the bacterium, virus, fungus or other pathogen responsible for an infection. The hunt is often slow and laborious, and the processes used may not be broad enough in scope to find specific disease agents.
One solution may be next-generation sequencing (NGS), according to the findings of a recent study by Johns Hopkins Medicine researchers. NGS enables clinicians to simultaneously sequence multiple strands of DNA found in patient samples and use that analysis to rapidly and accurately identify a single pathogen — from among hundreds of suspects.
In a paper first posted online June 13, 2022, in the American Society for Microbiology’s Journal of Clinical Microbiology, the researchers compared the pathogen detecting ability of an NGS system — the Respiratory Pathogen Infectious Diseases/Antimicrobial Resistance Panel (RPIP) — with a previously studied NGS system and standard of care (SOC) diagnostic methods for samples obtained with bronchoalveolar lavage. This is where a bronchoscope is passed through the mouth or nose into the lungs, followed by a fluid wash that is collected for examination.
The researchers believe their study is among the first to compare NGS and SOC diagnostics for respiratory pathogens.
“We evaluated the two NGS diagnostic techniques, one of which was the RPIP, and found that in both cases, the ability of NGS to identify specific pathogens was nearly comparable to the battery of diagnostic tests clinicians have been using for decades,” says study senior author Patricia Simner, Ph.D., M.Sc., associate professor of pathology at the Johns Hopkins University School of Medicine. “Although this shows great promise for the RPIP and NGS diagnostics in general, we feel more work is needed to further refine the technology before NGS can be considered equal to or better than current SOC methods.”
In their study, Simner and her colleagues first evaluated the diagnostic ability of metagenomic NGS, a previously studied workflow process during which all DNA obtained from a bronchoalveolar lavage is sequenced — including genetic material unique to the patient (the “host read” or “human read”) and the sought-after pathogen (the “microbial read”). Removing the host DNA enable clinicians to concentrate their search on the remaining genetic material to hopefully find the microbial read and ultimately, identify the cause of the patient’s illness.

Banana peels aren’t always destined for the trash or compost anymore. They’re making their way onto people’s plates, replacing pork in “pulled peel” sandwiches and getting fried up into “bacon.” And now, researchers reporting in ACS Food Science & Technology show that incorporating banana peel flour into sugar cookie batter makes the treats more healthful. In taste tests, cookies enriched with some banana peel flour were more satisfying than those baked with wheat flour alone.
Interest in plant-based diets and reducing food waste is increasing, and people want creative ways to use every part of their vegetables and fruits. Banana peels are one such waste that chefs and home cooks have been experimenting with, but these skins are extremely fibrous, making them unpleasant to eat raw. Recently, scientists found that they can grind the peels into a flour that’s rich in fiber, magnesium, potassium and antioxidant compounds. And when small amounts of wheat flour in breads and cakes were replaced with the new flour, the baked goods were more nutritious and had acceptable flavors. However, similar experiments haven’t been widely done with cookies. So, Faizan Ahmad and colleagues wanted to substitute some of the wheat flour in sugar cookies with banana peel flour, assessing the cookies’ nutritional quality, shelf-stability and consumer acceptance.
To make banana peel flour, the researchers peeled ripe, undamaged bananas and then blanched, dried and ground the skins into a fine powder. They mixed together different amounts of the powder with butter, skimmed milk powder, powdered sugar, vegetable oil and wheat flour, creating five batches of sugar cookies, and baked them.
Increasing the amount of the banana peel flour from 0 to 15% in the batches produced browner and harder products, which could be a result of the increased fiber content from the peels. In addition, cookies with banana peel flour were more healthful, having less fat and protein, higher amounts of phenols and better antioxidant activities than the conventional ones. A trained panel determined that cookies with the smallest substitution of banana peel flour (7.5%) had the best texture and highest overall acceptability compared to the other batches. This batch also kept well for three months at room temperature — it tasted the same as the wheat-only versions after the lengthy storage period. Because cookies can be enriched with some banana peel flour without impacting their consumer acceptance, the researchers say this addition could make these baked goods more nutritious.
The authors acknowledge funding from the Department of Post-Harvest Engineering and Technology, Faculty of Agricultural Sciences, Aligarh Muslim University.
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The model, described today in eLife, may help improve outcomes for patients with postmenopausal osteoporosis and reduce the risks of side effects by helping physicians build more personalised treatment regimes.
The sudden loss of the hormone oestrogen during menopause can interfere with the body’s natural processes for repairing natural wear and tear on bones, leading to more weakened bones and possible fractures. Several drugs are available to treat this type of postmenopausal bone loss. While these treatments can be combined, there is little evidence to suggest what the most effective combinations might be.
“We wanted to know if there are treatment combinations that would work considerably better than those tested and currently used in clinical practice,” says first author David Jörg, Senior Scientist in the Biomedical Modeling and Simulation Group, Fresenius Medical Care Germany, Bad Homburg, Germany. “If so, then this could be beneficial for treating a large number of osteoporosis patients by increasing their bone strength and reducing their risk of bone fracture risk more than standard therapies currently allow.”
To explore this further, Jörg and colleagues built a mathematical model of bone renewal that predicts the effects of various osteoporosis medications in postmenopausal women. They based the model on the latest evidence of how old bone breaks down and new bone is created, as well as how different classes of osteoporosis medications work. They then verified the accuracy of the model by testing its predictions on data from clinical trials.
Next, the team tested the effects of reshuffling the order of different osteoporosis medications. Their model showed that some combinations in a particular order would perform significantly better than others. They also found that combinations that cause the most rapid increases in bone density do not always strengthen bone in the long term and can instead cause a rebound of accelerated bone loss after the treatment stops. “These results show us why the order in which osteoporosis medications are taken is important for short and long-term treatment success in patients,” says co-author Doris Fürtinger, Director of the Biomedical Modeling and Simulation Group, Fresenius Medical Care Germany.
While the model was specific to postmenopausal women, the authors say it could be adapted to help design treatment combinations for patients with bone loss caused by other medications or medical conditions. For example, it could be beneficial for those who take corticosteroid medications or who have hyperparathyroidism and gastrointestinal diseases.
“As our model could potentially predict the effects of a broad range of complex drug combination therapies beyond those used for its development, it could be used for the design of future clinical trials,” says senior author Peter Kotanko, Research Director at the Renal Research Institute, New York, US, and Adjunct Professor of Medicine and Nephrology at the Icahn School of Medicine at Mount Sinai, New York.
Kotanko adds that general limitations of the model need to be considered when using it as a predictive tool, especially when applying the data to extreme dosing regimens, dosing frequencies or age regions beyond those validated in the study. “However, we’ve shown that not only can the model be used as a starting point for forecasting osteoporosis therapy success, but it also highlights the role of mathematical descriptions in helping us understand the biological principles of how drugs work,” he concludes.
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A research team at the University of Oklahoma published a study in the journal Advanced Science that presents a new approach to triggering an adaptive immune response.
The study was led by Handan Acar, Ph.D., the Peggy and Charles Stephenson Assistant Professor of Biomedical Engineering in the Gallogly College of Engineering, with collaborators in the Department of Microbiology and Immunology at the OU Health Sciences Center Mark Lang, Ph.D., and Susan Kovats, Ph.D., who is also a researcher at the Oklahoma Medical Research Foundation. Doctoral student Gokhan Gunay is the first author of the paper.
How Cell Death Causes an Immune Response
It might sound violent, but cell death is an important biological process. Immunogenic cell death occurs when cells are under stress and their membranes are damaged. Besides pathogens — microscopic disease-causing organisms — innate immunity is responsive to what scientists call “Damage-Associated Molecular Patterns,” or DAMPs. These so-called “danger molecules” are released from stressed or dying cells to alert the body to impending danger. When under stress, cells induce the DAMPs danger signals to alert the immune system to the location in the body where the stress is being experienced.
“Cell membrane damage can be accidental because of a physical force like a cut or burn or programmed because of a virus or bacteria, and that damage induces DAMPs release,” Acar said. “For example, if there is an infection in a cell, the pathogen might use the resources in the cell and drive its stress and slow death. The stressed cells release signals to the immune system, which also triggers programmed cell death. Depending on the amount of damage and the duration of time the danger signals are being sent, the immune response increases.”
There are two kinds of immune responses, innate and adaptive. Innate immunity offers initial protection to a virus or bacteria that originated outside of a body, but it is not specific. Through this DAMPs response process, the innate immune system absorbs pathogens and teaches cells adaptive immunity. Put another way, adaptive immunity comes from the body learning over time and creating antibodies specific to those pathogens.