Publisher Health

Colorectal tumors are swarming with white blood cells, but whether these cells help or hinder the cancer is hotly debated. While some studies have shown that white blood cells heroically restrict tumor growth and combat colorectal cancer, equally compelling evidence casts the white blood cells as malignant co-conspirators — bolstering the tumor and helping it spread.
Now, new research clarifies the role of these intestinal white blood cells, known as 𝛄𝛅 T cells, in colorectal cancer. It turns out that the cells have a double-edged function: They rein in early-stage tumors but, as the disease progresses, undergo biochemical changes and switch sides, strengthening the tumor. The findings, published in Science, shed further light on the role of 𝛄𝛅 T cells in tumor growth, and may open new paths toward colorectal cancer therapies.
“𝛄𝛅 T cells that live in the gut act to prevent tumor formation,” says Bernardo Reis, a research associate in the laboratory of Daniel Mucida at The Rockefeller University. “But once tumors form, gut 𝛄𝛅 T cell populations change, enter the tumor, and promote tumor growth.”
Altered T cell receptors
The intestinal lining may be the body’s most vulnerable port of entry. Composed of but a single layer of epithelial cells, this busy digestive region must absorb useful substances like nutrients, and reject harmful ones like foodborne pathogens, within a limited working space. 𝛄𝛅 T cells mind the gaps, perpetually scanning the epithelium to maintain the integrity of the intestinal lining and prevent pathogens from invading the rest of the body.
Reis set out to investigate conflicting claims over whether these cells help or hinder the growth of intestinal tumors. But as is often the case in biology, there was no simple answer.

To act as a robust barrier against pathogens while also absorbing needed nutrients, the lining of the intestines must regenerate on a daily basis to remain equal to the task. The intestine’s resident stem cells are responsible for meeting this need for constant repair and replenishment, but each stem cell faces decisions that depend on the overall conditions of the intestine and the needs of the moment. Bad decisions and poor coordination could result in intestinal diseases or cancer.
A new study suggests that stem cells are able to integrate cues from their surroundings and coordinate their behavior across the tissue through networks of vasculature in their close vicinity.
Rockefeller scientists found that lymphatic capillaries — fine vessels that transport immune cells and drain fluids from tissues — represent a signaling hub that communicates with stem cells to regulate their activity. With molecular guidance from the lymphatics, the stem cells produce daughter cells to repopulate the intestinal lining or self-renew to restock the stem cell reserve.
The findings, published in the journal Cell Stem Cell, provide new insights about primary intestinal components whose disrupted communication may contribute to intestinal disorders, such as inflammatory bowel disease. “The key to treating these diseases will be to figure out who talks to whom in this ecosystem and how we can reset the communication networks,” says Rachel Niec, a clinical scholar in the laboratory of Elaine Fuchs.
Communications in the crypt
The intestinal stem cells reside in so-called crypts, found at the base of densely packed indentations in the intestinal lining. The stem cells may renew and stay in the crypt, or differentiate into specialized cells, which then migrate out of the crypt to replenish the gut lining. “To understand how stem cells balance self-renewal with differentiation, we needed a more complete picture of crypt niches,” says Marina Schernthanner, a graduate student in the Fuchs lab.
To zoom in on the crypt, the team used a suite of techniques, including single-cell and spatial transcriptomics, which allowed them to identify cell types at specific locations and study their signaling molecules. The results showed that lymphatic capillaries, which form an intimate connection with the stem cells in the crypt, produce a number of proteins known to be important for stem cell functioning.
One previously underappreciated protein, REELIN, emerged as a top candidate for mediating communications between lymphatics and stem cells. By manipulating the amount of REELIN in lab-grown intestinal organoid cultures in some experiments and genetically suppressing it in mice in others, the researchers found that REELIN directly governs the regenerative behavior of intestinal stem cells.
The involvement of the lymphatic system in stem cell functioning is a relatively new concept. A previous study by the Fuchs team revealed that lymphatics are also closely involved with stem cells of the skin and play a key role in hair regeneration. There, however, it is the hair follicle stem cells that signal to lymphatic capillaries. By controlling their interactions with lymphatics, the stem cells synchronize hair regeneration across the tissue. “This suggests that lymphatics may be a conserved feature of stem cell niches, but their relationship to stem cells are likely tailored around the needs of each tissue,” Niec says.
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New research by Georgia State University’s TReNDS Center may lead to early diagnosis of conditions such as Alzheimer’s disease, schizophrenia and autism — in time to help prevent and more easily treat these disorders. In a new study published in Scientific Reports a team of seven scientists from Georgia State built a sophisticated computer program that was able to comb through massive amounts of brain imaging data and discover novel patterns linked to mental health conditions. The brain imaging data came from scans using functional magnetic resonance imaging (fMRI), which measures dynamic brain activity by detecting tiny changes in blood flow.
“We built artificial intelligence models to interpret the large amounts of information from fMRI,” said Sergey Plis, associate professor of computer science and neuroscience at Georgia State, and lead author on the study.
He compared this kind of dynamic imaging to a movie — as opposed to a snapshot such as an x-ray or, the more common structural MRI — and noted “the available data is so much larger, so much richer than a blood test or a regular MRI. But that’s the challenge — that huge amount of data is hard to interpret.”
In addition, fMRI’s on these specific conditions are expensive, and not easy to obtain. Using an artificial intelligence model, however, regular fMRI’s can be data mined. And those are available in large numbers.
“There are large datasets available in individuals without a known clinical disorder,” explains Vince Calhoun, Founding Director of the TReNDS Center, and one of the study’s authors. Using these large but unrelated available datasets improved the model’s performance on smaller specific datasets.
“New patterns emerged that we could definitively link to each of the three brain disorders,” Calhoun said.

A first-of-its-kind sprayable coating that can prevent the surface spread of infection from bacteria and viruses — including COVID-19 — over a sustained period — has been developed by a team of Australian researchers.
Described in the journal Advanced Science, the spray works two ways: repelling viruses and bacteria through an air-filled barrier, and killing pathogens through microscopic materials if the layer becomes damaged or submerged for extended periods. The spray uses a combination of plastics strong enough to be considered an alternative to bullet-proof glass.
The coating provides a reliable alternative to standard disinfectants, which are becoming less effective and require regular reapplication, and is the only permanent surface layer proven to protect surfaces from contamination by viruses. It is safer than existing alternatives to disinfectant, with no harmful side effects and more stable potency — unlike the next most promising non-disinfectant agent that kills bacteria, silver nanoparticles.
The authors said the coating could be applied to surfaces in public settings such as lift buttons, stair rails, surfaces in hospitals, nursing homes, schools and restaurants, to prevent the spread of common viruses and bacteria.
Co-lead author University of Sydney’s School of Biomedical Engineering Professor Antonio Tricoli and Director of the University of Melbourne’s Graeme Clark Institute, Professor David Nisbet said the spread of viral and bacterial pathogens through contact with surfaces is a leading cause of infection worldwide. Surface contamination also plays a major role in the evolution of antibiotic-resistant bacterial strains.
“Without a barrier, viruses such as coronaviruses can stay on surfaces and remain infectious for up to a week. Other viruses such as reoviruses, which can cause colds or diarrhoea, for instance, can remain on surfaces for several weeks, causing large outbreaks in health and aged care facilities,” Professor Tricoli said.

Nearly 6 percent of children who presented to the Emergency Department (ED) with COVID-19 reported symptoms of long COVID 90 days later, according to a study conducted in eight countries and published in JAMA Network Open. Initial hospitalization of 48 or more hours, four or more symptoms at the initial ED visit, and age 14 years or older were associated with long COVID.
“We found that in some children, illness with COVID-19 is associated with reporting persistent symptoms after 3 months,” said Principal Investigator Stephen Freedman, MDCM, MSc, with the Cumming School of Medicine at University of Calgary, and Alberta Health Services. “Our results suggest that appropriate guidance and follow-up are needed, especially for children at high risk for long COVID.”
The study included 1,884 children with COVID-19 who had 90-day follow-up. Long COVID was found in nearly 10 percent of hospitalized children and 5 percent in children discharged from the ED.
“Reported rates of long COVID in adults are substantially higher than what we found in children,” said Co-Principal Investigator Nathan Kuppermann, MD, MPH, from University of California, Davis School of Medicine, Sacramento. “Our findings can inform public health policy decisions regarding COVID-19 mitigation strategies for children and screening approaches for long COVID among those with severe infections.”
The most reported persistent symptoms in children were fatigue or weakness, cough, difficulty breathing or shortness of breath.
“Our finding that children who had multiple COVID-19 symptoms initially were at higher risk for long COVID is consistent with studies in adults,” said Co-Principal Investigator Todd Florin, MD, MSCE, from Ann & Robert H. Lurie Children’s Hospital of Chicago and Northwestern University Feinberg School of Medicine. “Unfortunately, there are no known therapies for long COVID in children and more research is needed in this area. However, if symptoms are significant, treatment targeting the symptoms is most important. Multidisciplinary care is warranted if symptoms are impacting quality of life.”
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One of the greatest challenges facing cancer researchers is to understand why some patients don’t respond to treatments. In some cases, tumors exhibit what is known as multidrug resistance (MDR), which significantly limits the therapeutic options for patients. Researchers at the Spanish National Cancer Research Centre (CNIO) have discovered one of the causes of MDR, and a potential strategy to combat it. The work, which is mainly based on cell lines and is therefore still a long way from clinical use, is published in EMBO Molecular Medicine.
Our findings “explain why many of the available therapies don’t work in certain tumors, and at the same time identify the weak point of these resistant cancers,” explains Oscar Fernandez-Capetillo, head of the CNIO’s Genomic Instability Group and lead author of this research. “We now know that this vulnerability can be exploited using drugs that already exist.”
As the study shows, mutations that inactivate the function of a particular gene, FBXW7, “reduce the sensitivity to the vast majority of available therapies,” the authors write, but at the same time render tumor cells vulnerable to the action of a particular type of drug: those that activate the “integrated stress response” (ISR).
A very common mutation in human cancers
“FBXW7 is one of the 10 most frequently mutated genes in human cancers,” and is associated with “poor survival across all human cancers,” the authors add.
The study began by using the CRISPR technology in mouse stem cells to search for mutations that generate resistance to anti-tumoral agents such as cisplatin, rigosertib or ultraviolet light. Mutations in the FBXW7 gene emerged early on, suggesting that this mutation could confer MDR. Bioinformatic analysis of databases such as the Cancer Cell Line Encyclopedia (CCLE), with information on the response of more than a thousand human cancer cell lines to thousands of compounds, confirmed that FBXW7 mutant cells are resistant to most of the drugs available in this dataset.

A study published in the journal Pharmacological Research reveals the oligomeric molecular structure of the MOR-Gal1R complex, a component present in the brain which is involved in the analgesic and addictive effects of certain opioids. The study includes the participation of the experts Vicent Casadó, Estefanía Moreno and Verònica Casadó-Anguera, from the Molecular Neuropharmacology Research Group of the Faculty of Biology and the Institute of Biomedicine of the University of Barcelona (IBUB).
The study is coordinated by the experts Vicent Casadó (UB-IBUB), Leonardo Pardo (UAB), Leigh Daniel Plant (Boston Northeastern University, United States) and Sergi Ferré (National Institute on Drug Abuse, NIH, United States).This preclinical study, based on the use of cellular models and leading biophysical, biochemical and pharmacological techniques (total internal reflection fluorescence microscopy, TIRF), has been distinguished for its scientific interest in the website of the NIH’s National Institute on Drug Abuse.
Receptors, macrostructures and pharmacological activity
Gal1R and MOR receptors belong to the family of G protein-coupled receptors (GPCRs) that take part in the transduction of different cellular signals and the control of essential cell functions. These structures can form dimers — homodimers or heterodimers — that determine functional and pharmacological properties that are different from those of the individual components.
The study shows different in vitro evidences that reveal the preference of Gal1R and MOR receptors to form homodimeric complexes (MOR-MOR or Gal1R-Gal1R) in cell cultures when they are expressed separately. When expressed together, tetrameric complexes (heterotetramers) are formed by homodimers of both receptors (MOR-MOR-Gal1R-Gal1R-Gal1R).
“This heterotetrameric structure is even more complex because when the homodimers of both receptors join to form the MOR-MOR macrocomplex, the interaction and corresponding signalling is maintained by means of their characteristic G protein (the G protein inhibitory to adenylate cyclase or Gi),” says Vicent Casadó, member of the Department of Biochemistry and Molecular Biomedicine and the IBUB.
“However, Gal1R-Gal1R exchanges its characteristic inhibitory G-protein for the adenylyl cyclase-stimulating G-protein (Gs). This higherorder oligomeric complex contains more than 10 protein subunits considering the four receptors, the two heterotrimeric G-proteins and the adenylyl cyclase enzyme on which both G-proteins act to up- or down-regulate the intracellular levels of the cyclic AMP messenger,” adds the expert. Determining the molecular characteristics of this macrostructure would explain the molecular mechanism by which the neuropeptide galanin — which has neurotrophic and neuroprotective properties — causes a decrease in the release of dopamine into the nucleus accumbens induced by opioids, as described by the same team (Journal of Neuroscience, 2016).
“This would be possible because when the Gal1R ligand binds to the heteromer, it activates the Gs protein, which interacts with the same adenylyl cyclase that was inhibited by the MOR-activated Gi protein, so it counteracts the secondary effects that opioid ligands have in activating the MOR receptors in the ventral tegmental area,” says researcher Estefanía Moreno, member of the Department of Biochemistry and Molecular Biomedicine and IBUB.
Searching for new non-addictive drugs
In previous studies, the team from the Faculty of Biology and the IBUB had already showed that the greater proportion of analgesic — and not euphoric — effects of methadone administration make this compound the most indicated non-addictive option for the treatment of chronic pain (Journal of Clinical Investigation, 2019). This could be explained by the fact that methadone acts preferentially on MOR receptors when they do not form heteromers with Gal1R receptors, and therefore, its effect is mainly peripheral.
“Now, knowing this tetrameric macrostructure of the receptor complex — in addition to the differential capacities of opioid ligands to activate MOR depending on the formation of oligomeric complexes with other receptors — will facilitate the future design of opioid drugs that can bind with a greater affinity or can bind more effectively the signal pathways with mu-opioid receptor homodimers than with the MOR-Gal1R heterotetramers,” notes researcher Verònica Casadó-Anguera.
Specifically, it would be about μ-opioid receptor drugs capable of discriminating between homodimers of these compounds and their heterotetramers with galanin receptors. “It is also possible to design a strategy that combines opioid ligands with Gal1R ligands that bind to the heterotetramer and inhibit the activation of the dopamine system and, therefore, addiction. Thus, these therapies are expected to have a greater analgesic effect and less addictive activity,” concluded the research team.

The Omicron variants BA.1 and BA.2 of the SARS-CoV-2 virus, which dominated from about December to April, can already circumvent after three months the protection against infection offered by vaccinations and recovery from infection. This has been revealed in a study in Frankfurt lead-managed by University Hospital Frankfurt and Goethe University. Moreover, according to the study, various pharmaceutical antibody preparations (monoclonal antibodies) have widely differing effects on the two virus variants. The study authors emphasise how important it is to align protective measures to the genetic changes in the virus, therefore.
The Omicron variant of the SARS-CoV-2 virus was first detected in South Africa in November 2021. The high level of infectiousness of the virus and its ability to quickly spawn additional variants has also been observed in Germany: Since January 2022 the Omicron variant BA.1 has dominated here, followed in subsequent months by the variant BA.2. In the meantime, the virus has mutated further, and since June the variants BA.4 and BA.5 have superseded their predecessors.
This poses major challenges for the immune system of the human body: antibodies are formed in the course of a SARS-CoV-2 infection and these attach themselves to the surface structures of the virus, thus preventing it from penetrating human cells. The viral spike protein plays the key role here. In the Omicron variants, this has changed in more than 50 sites compared to the first SARS-CoV-2 virus identified in Wuhan. The consequence: the antibodies formed after an infection or a vaccination do not recognise the variants less efficient. This is why despite having overcome an infection, people can again become infected with a new SARS-CoV-2 variant, or there are breakthrough infections. However, how good the immunity response is to an infection depends on more than just antibodies.
Researchers in Frankfurt headed by Marek Widera and Professor Sandra Ciesek from the Institute for Medical Virology at the University Hospital of the Goethe University Frankfurt have now examined how long the antibodies present in blood after a vaccination or recovery from an infection were still able to neutralise the virus variants Omicron BA.1 and BA.2. To this end, they collected blood samples from people who had been vaccinated twice or three times (booster shot), placed the liquid blood component (blood serum), which contains antibodies, together with SARS-CoV-2 viruses on cultivated cells and observed how many of the cells became infected. Furthermore, in each case they ascertained the quantity of antibodies in the samples that recognised the spike protein.
The result: six months after the second vaccination, the tested sera practically had no neutralising effect on the Omicron variants BA.1 and BA.2. The effect of a booster vaccination declined rapidly: although the sera still provided very good protection shortly after the booster vaccination, three months later the protective effect was merely very weak, with the effect that the tested sera were no longer capable of neutralising the two virus variants. “This is due to the fact that the antibody titre in serum — the amount of antibodies, so to speak — after a vaccination or infection declines in the course of time,” explains Widera. “Because the antibodies have a significantly lower ability to recognise newer virus variants, a lower level of antibodies is then no longer sufficient to neutralise the virus variants and prevent an infection of the cells in a cell culture. However, the data from this study does not allow any conclusions to be drawn regarding protection against the seriousness of the course of the disease.” The decisive factor for the immune function is not just the antibody titre, but also the cellular immune response, which was not examined in this study, Widera adds.
These results are particularly problematic for the use of monoclonal antibodies, which are administered to patients with a compromised immune system as a precautionary measure, for example, says Professor Sandra Ciesek. Ciesek is the Director of the Institute for Medical Virology at the University Hospital Frankfurt and the senior author of the study. She explains: “As an example we studied three such monoclonal antibodies in laboratory experiments and saw that their efficacy is very heavily dependent on the virus variant. So that we are able to protect vulnerable patients with such preparations, it is absolutely essential to also test in patients the extent to which such antibodies can neutralise the virus variants that are currently prevalent, therefore.” Admittedly, the virus variants BA.1 and BA.2 examined in the study are no longer dominant in Germany in the meantime, adds the virologist. “Our study shows, however, that we cannot afford to let up in adapting our protective measures in line with the genetic changes in the SARS-CoV-2 virus, at present to the Omicron variants BA.4 and BA.5, therefore.”
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Researchers have successfully tested a device that may one day use the chemical biomarkers in sweat to detect changes in a person’s health.
In a new study published in the journal Science Advances, a team from The Ohio State University demonstrated a battery-free, wireless biochemical sensor that detected the blood sugar — or glucose — humans excrete from their skin when they exercise.
The Ohio State team fabricated a “smart necklace” — complete with a functional clasp and pendant — which, once placed around their necks, was used to monitor the glucose level of study participants as they exercised.
Instead of a battery, it works using a resonance circuit, which reflects radio frequency signals sent out by an external reader system. After engaging in indoor cycling for 30 minutes, participants took a 15-minute break, during which they drank sugar-sweetened beverages, before resuming cycling.
The researchers knew that glucose levels in the sweat should rise after drinking the sugary beverages — the question was whether this new sensor would pick it up, said Jinghua Li, co-author of the study and assistant professor of materials science and engineering at Ohio State.
The results showed the sensor did track the glucose levels successfully, which suggests it will work to monitor other important chemicals in sweat.

For patients with lymphoma, multiple myeloma, or certain types of leukemia, treatment with chimeric antigen receptor T cells (CAR T cells) is sometimes the last chance of overcoming the cancer. The treatment involves taking T cells from the patient’s blood and adding artificial receptors — the CARs — to them in the lab. As the guards of our immune system, T cells are on permanent patrol in our blood vessels and tissues, where they hunt down foreign structures. Equipped with CARs, T cells can also detect very specific surface structures on cancer cells. Once the CAR T cells are returned to the patient by infusion, they circulate in the body as a kind of living drug that can bind to very specific tumor cells and destroy them.
The engineered immune cells remain in the body permanently and multiply. If the cancer flares up again, they’ll go back into action. That’s the theory, at least. But in practice, many patients still relapse. This is because the tumor cells can outwit the CAR T cells by producing more of the protein EBAG9 — and by causing the T cells to produce more of it, too. In T cells, EBAG9 inhibits the release of cytotoxic enzymes, which slows the desired immune response.
A month earlier, a team led by last authors Dr. Armin Rehm and Dr. Uta Höpken from the Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC) showed in the journal JCI Insight that shutting down the EBAG9 gene in mice led to a sustained increase in the immune response to cancer. The mice also developed more T memory cells. These cells are part of our immunological memory, which allows our immune system to respond better to a cancer antigen after encountering it previously.
Now the researchers have also shown these key findings in vitro, in human CAR T cells. Writing in Molecular Therapy, the team says that this is the decisive step on the road to therapeutic use. “Shutting down EBAG9 allows the body to eradicate tumor cells earlier and more radically. As well as achieving longer-lasting therapeutic success, this could also create a real chance of cure,” says Rehm.
Releasing the brake for immunotherapy
As soon as the EBAG9 gene was discovered, researchers recognized that it played an important role in cancer. But it took a long time to identify what that role actually was. When the MDC team started working on it in 2009, they found that mice without the gene dealt with bacterial and viral infections much better than mice with the gene, and that they formed more T memory cells, which are of particular interest in tumor biology.
Then in 2015, lead author Dr. Anthea Wirges succeeded in curbing synthesis of the EBAG9 protein using microRNA. For the latest study, she used microRNA to cultivate “EBAG9-silenced” CAR T cells with different human leukemia or lymphoma cells. Just like in the mouse model, the silencing reduced tumor growth much more. Relapses also only developed much later.
“Releasing the EBAG9 brake allows the genetically engineered T cells to release more cytotoxic substances. However, they don’t cause the strong cytokine storm that is typically a side effect of CAR therapy,” says Wirges. In fact, the risk is minimized because fewer cells are used. “Switching off the immune brake works across the board. We can do it with every CAR T cell that we produce — regardless of which type of blood cancer it targets.
Clinical studies are the next step
However, the first-line therapy for blood cancer will remain chemotherapy combined with conventional antibody therapy, as many patients respond very well to this. “CAR therapy only comes into play if the cancer returns. It’s very expensive because it’s an individual cellular product for a single person,” says Höpken. And a single treatment with that product can save a life.
The EBAG9 work shows how important perseverance and patience are for researchers. Wirges was motivated by the prospect of her work having a real chance of clinical application. Rehm adds: “Projects like this allow you to get to grips with a technique in basic research and then apply everything in translational research — right up to toxicological screening for the regulatory processes.” Their project has now reached this last stage: The researchers will present their concept to the Paul Ehrlich Institute, Germany’s biologics approval agency, in November.
Thanks to their findings from animal models and the in vitro experiments using human cells, the team now knows that releasing the EBAG9 brake is highly effective and doesn’t cause any more side effects than conventional CAR T therapy. “We now need bold clinicians and a partner for financing the clinical studies,” says Rehm. If everything goes well, the therapy using EBAG9-silenced CAR T cells could be available to patients in as little as two years’ time.