Allicin Can Inhibit SARS-CoV-2 Replication & Decrease Cellular Damage Caused By Infection (Biology)

Kirstin Mosbauer and colleagues in their recent paper showed that allicin efficiently inhibit SARS-CoV-2 replication and infectivity in Vero E6 and Calu-3 cell lines

There have been many drugs approved by FDA in clinical trials for treatment of COVID-19 like remdesivir, lopinavir/ritonavir and favipiravir. Apart from drugs, functional food based on herbal medicine is suggested as prophylaxis to prevent COVID-19 outcome due to their immunomodulatory, antioxidant, anticancer, antimicrobial and antiviral activities.

For example, garlic has been used for millennia in the treatment of a variety of human diseases and metabolic disorders. However, a review of the scientific literature suggests it could also have value as an inhalation therapy in the treatment of pulmonary infections caused by COVID-19 infection, and associated secondary bacterial infections, a significant cause of mortality in hospitalised patients.

Allicin, the principal active ingredient in garlic, has marked antimicrobial and antifungal properties and is active against many viruses including coronavirus (CoV) and severe acute respiratory syndrome coronavirus (SARS-CoV).

While the antiviral effect of allicin has been studied against several viruses that cause respiratory tract infections, including influenza, SARSCoV and rhinovirus, mechanistic insights on its proposed antiviral effects against SARS-CoV-2 in the infected host cell are lacking. Thus, Kirstin Mosbauer and colleagues now investigated the antiviral effect of allicin against SARS-CoV-2 in infected Vero E6 kidney cells and Calu-3 lung cells.

They found that, only the addition of 50 µM allicin to infected Vero E6 cells led to a significant 70% decrease in the amount of infectious virus particles, whereas, virus plaque assays and qRT-PCR results showed an almost complete >99% inhibition of SARS-COV-2 replication after exposure of 75 µM allicin, supporting the strong antiviral activity of allicin in infected Vero E6 cells.

Allicin protects Calu-3 cells against SARS-CoV-2 damage. SARS-CoV-2 induced cellular effects were studied in Calu-3 cells 24 h p.i. Calu-3 cells were infected with SARS-CoV-2 at a MOI of 0.01. At 24 h p.i., Calu-3 cells showed cellular damages, including cell rounding, detachment and cell death. Allicin treatment decreased the observed cellular damage significantly. Cells were imaged with a Nikon Ts2R-FL inverted microscope. © Mösbauer et al.

Additionally, the antiviral effects of biocompatible doses of allicin were analyzed in the human lung cell line Calu-3. After infection with SARS-CoV-2 at a multiplicity of infection (MOI) of 0.01 and 0.005, Calu-3 cells were treated with biocompatible doses of 100 and 200 µM allicin, respectively. It has been found that, the treatment of infected Calu-3 cells with 100 µM allicin did not significantly inhibit viral replication. However, exposure of infected Calu-3 cells to 200 µM allicin led to a significant >60 % decrease of viral RNA and a >65% reduction of infectious particles. These results were further supported by microscopy imaging in which, allicin partially protected the cells against the cellular damage of Calu-3 cells caused by SARS-CoV-2 infection.

“Taken together, our results show that allicin exerts a strong antiviral effect and inhibits SARS-CoV-2 replication in both the primate kidney-derived cell line Vero E6 and the human lung cell line Calu-3. In addition, the different allicin susceptibilities in these cell lines were caused by different intracellular Glutathione (GSH) levels”

Moreover, they used Label-free quantitative (LFQ) proteomics to further investigate the changes in proteome of Calu-3 cells caused by SARS-CoV-2 infection and the effect of allicin. They found that, allicin strongly affected virus-responsive expression of JAK/STAT, MAPK, PI3K/Akt and Ras signaling pathways, interferon (IFN) and interferon-stimulated gene (ISG) effectors, transcription, splicing, translation, ubiquitination, vesicular transport, tight junctions as well as glycan, lipid and nucleotide metabolism. Thus, their results confirm the antiviral and protective effect of allicin in host cells, supported by a decreased cellular damage of allicin-treated infected Calu-3 cells.

“Allicin exerts a beneficial effect as an antiviral and immunomodulatory compound in cell lines and could be utilized as a supportive therapy for the treatment of COVID-19.”

— concluded authors of the study

Featured image: Schematic of viral RNA recognition, activation of the IFN and ISG signaling pathways (A) and antiviral functions of the identified ISG effectors (B). A) SARS-CoV-2 enters host cells via endocytosis. RIG-I is a cytosolic receptor to recognize viral RNA. cGAS and OAS are ISG effectors that function as RNA sensors. RIG-I, IFIH and cGAS activate the mitochondrial antiviral-signaling protein (MAVS) and stimulator of IFN genes (STING), leading to phosphorylation of IFN responsive factors (e.g. IRF3), followed by IRF3 dimerization, translocation into the nucleus and transcriptional activation of IFN expression. IRF3 is negatively regulated by IFI44. RIG-I, MAVS and STING can be regulated by ubiquitination (UBE2) and ISGylation (ISG15). Type-I IFN a/ß bind to the IFNAR receptor, resulting in phosphorylation of signal transducers and activators of transcription (STAT1/2) by the JAK and TYK kinases. Phosphorylated STAT1/2 form dimers and bind to IRF9, which triggers transcription of IFN-stimulated genes (ISGs) in the nucleus. B) Antiviral ISG effectors affect different stages of the viral life cycle. Mx1 inhibits virus endocytosis and uncoating of the ribonucleocapsid. IFI16, OAS and IFIT function in viral RNA degradation and block translation. IFIT, ISG15, TRIM and UBEL inhibit transcription, replication, translation or virus assembly. FKBP4 promotes protein folding. Kinesins (KIFA/B/C), Clathrin (CLTCL1) and TUBAL3 are involved in transport of virus vesicles. ARHGAP17 facilitates the formation or repair of tight junctions. © K. Mösbauer et al.

Reference: Kirstin Mösbauer, Verena Nadin Fritsch, Lorenz Adrian, Jörg Bernhardt, Martin Clemens Horst Gruhlke, Alan John Slusarenko, Daniela Niemeyer, Haike Antelmann, “Allicin inhibits SARS-CoV-2 replication and abrogates the antiviral host response in the Calu-3 proteome”, bioRxiv 2021.05.15.444275; doi:

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Accelerators Meet Gravitational Waves (Physics)

Physicists discuss the possibility of using particle accelerators to detect or even generate gravitational waves

In particle accelerators like the Large Hadron Collider (LHC), charged particles bob and weave in magnetic and electric fields, following tightly corralled trajectories. Their paths are computed assuming a flat Euclidean space-time, but gravitational waves ­– first observed by the LIGO and Virgo detectors in 2015 – crease and stretch this underlying geometry as they ripple out across the universe. For the past 50 years, there has been intermittent interest in the possibility of detecting observable resonant effects as a result of this extra curvature of the fabric of space-time, as the particles whizz around the accelerators repeatedly at close to the speed of light.

Advances in accelerator technology could now usher in an era of gravitational-wave astronomy in which particle accelerators play a major role. To explore this tantalising possibility, over 100 accelerator experts, particle physicists and members of the gravitational physics community participated in a virtual workshop entitled “Storage Rings and Gravitational Waves” (SRGW2021), organised as part of the European Union’s Horizon 2020 ARIES project. During this meeting, they explored the role that particle accelerators could play in the detection of cosmological backgrounds of gravitational waves. This would provide us with a picture of the early universe and give us hints about high-energy phenomena, such as high-temperature phase transitions, the nature of inflation and new heavy particles that cannot be directly produced in the laboratory.

Lively discussions at the SRGW2021 workshop – the first, apart from an informal discussion at CERN in the 1990s, to link accelerators and gravitational waves and bring together the scientific communities involved – attest to the prospective role that accelerators could play in detecting or even generating gravitational waves. The great excitement and interest prompted by this meeting, and the exciting preliminary findings from this workshop, call for further, more thorough investigations into harnessing future storage rings and accelerator technologies for gravitational-wave physics.

This text was extracted from the full meeting report in CERN Courier, where you can learn more about gravitational-wave research using particle accelerators.

Provided by CERN

FASER Catches First Candidate Collider Neutrinos (Particle Physics)

The result paves the way for studies of high-energy neutrinos at current and future particle colliders

It’s a first at the Large Hadron Collider (LHC), or indeed at any particle collider: the FASER collaboration has detected the first candidate particle interactions for neutrinos produced in LHC collisions. The result, described in a paper posted online, paves the way for studies of high-energy neutrinos at current and future colliders.

Neutrinos are the most abundant fundamental particles that have mass in the universe, and they have been detected from many sources. Yet, no neutrino produced at a particle collider has ever been directly detected, even though colliders produce them in abundance. Studying such collider neutrinos could shed new light on the still enigmatic nature of these fundamental particles, not least because collider neutrinos are produced at high energies, at which their weak interactions with matter have been little studied.

The FASER experiment’s FASERν detector and the newly approved SND@LHC detector have both been designed to catch and study collider neutrinos, and they are expected to be installed at the LHC over the course of 2021 and to begin taking data when the collider starts up again in 2022. However, the FASER collaboration was in for an early treat when it took four weeks’ worth of proton–proton collision data with a smaller pilot version of FASERν shortly before the LHC was shut down for maintenance and upgrades at the end of 2018.

After analysing the pilot detector data and estimating a background of particle events that could mimic the signal from neutrino interactions, the FASER team found several candidate events for collider neutrinos. The result has a statistical significance of 2.7 standard deviations, a little below the 3 standard deviations required to claim evidence of a particle or process in particle physics.

“The goal of the pilot detector was to demonstrate the feasibility of neutrino measurements in the experimental environment of the LHC,” says FASER co-spokesperson Jamie Boyd. “So we are very excited that this small detector, which is only about 1% of the final detector, allowed us to see the first candidate events for neutrino interactions at a collider.”

The team expects to observe about 20 000 collider neutrino interactions with the full-fledged FASERν detector in the next LHC run, from 2022 to 2024.

Shows particle tracks from neutrino interactions
Two candidate events for neutrinos produced in LHC collisions and interacting in the FASERν pilot detector. The neutrinos enter the detector from the left, and interact with the detector material to produce a number of charged particles. The different lines in each event show tracks from these charged particles, originating from the neutrino interaction point. (Image: FASER/CERN)

Featured image: The FASER experiment in the LHC tunnel. (Image: CERN)

Reference: FASER Collaboration, “First neutrino interaction candidates at the LHC”, Arxiv, 2021.

Provided by CERN

Protecting the IQ Of People At Risk For Psychosis (Psychiatry)

A UNIGE team has found that a class of drugs can protect the development of intellectual abilities in people at risk of psychosis, if prescribed before adolescence.

One person in 2000 suffers from a microdeletion of chromosome 22 that can lead to the development of psychotic disorders, such as schizophrenia, in adolescence. In addition to symptoms such as hallucinations or delusions, psychotic disorders also comes with a progressive decline in intelligence quotient (IQ). If current drug treatments are successful in containing psychotic symptoms, nothing can be done to prevent the deterioration of intellectual skills that leads to loss of autonomy. Researchers at the University of Geneva (UNIGE), Switzerland, have discovered that prescription of selective serotonin reuptake inhibitors (SSRIs) – a class of drugs used to treat anxiety and depression –in late childhood can reduce the deterioration of intellectual abilities, and have a neuroprotective effect on some of the brain regions affected by the psychotic illness. This study, to be read in the journal Translational Psychiatry, opens up a new field of research and new hope for people affected by the microdeletion of chromosome 22.

The average IQ is around 100 points. However, for people who may develop a psychotic illness, such as those with a microdeletion of chromosome 22, the average drops to 70-80 points. “The problem is that when a psychotic disorder occurs, such as schizophrenia, the brain frontal lobe and the hippocampus are particularly affected, which leads to the gradual deterioration of already below-average intellectual capacities”, explains Valentina Mancini, a researcher in the Department of Psychiatry at UNIGE Faculty of Medicine and first author of the study. From then on, the average IQ drops to around 65-70 points, leading to a loss of autonomy that requires a protected environment. “At present, drug treatments manage to contain psychotic symptoms, such as hallucinations, anxiety or distortion of reality, but there is no treatment that can reduce the deterioration of affected people’s intellectual capacities”, notes the Geneva researcher.

200 patients followed over a 20 years period reveal a possible solution

The team of Stéphan Eliez, professor in the Department of Psychiatry at UNIGE Faculty of Medicine, has been following 200 patients affected by the microdeletion of chromosome 22 for the past 20 years. “30 to 40% of them developed schizophrenia psychotic disorder”, he explains. “Thanks to this cohort, we found that people suffering from this syndrome lost 7 to 8 IQ points from childhood to adulthood. This figure rises to 15 IQ points for those who developed psychotic disorders.”

Yet the physicians noted that two to three teenagers a year are exceptions, and even gained IQ points. Why? “We made a comprehensive analysis of these patients’ medical data to find out any common feature in the treatments prescribed to them by their GP”, explains Valentina Mancini. Two observations caught their attention.

The first is the prescription of small, regular doses of SSRIs –  a drug that increases the levels of serotonin, a neurotransmitter involved in the regulation of behaviour – in late childhood and throughout adolescence. “These drugs increase neurogenesis and act on synaptic plasticity. They are prescribed today to reduce anxiety and depressive symptoms”, explains the Geneva researcher. And the younger the patients received this treatment, at around 10-12 years of age, the more the frontal lobe and the hippocampus – and therefore the intellectual capacities – were preserved from deterioration caused by the psychotic illness. The second observation is that a neuroleptic drug – prescribed in small doses to control psychotic symptoms such as hallucinations or delusions – also seems to have a positive effect if added to SSRIs during adolescence. “These two medications, especially when combined, have thus preserved the anatomical structure of the brain affected by the degradation responsible for the decline in intellectual capacity”, remarks Stéphan Eliez.

A promising discovery for the future of people at risk of psychosis

This study provides for the first time an indication of a neuroprotective preventive treatment for the development and preservation of IQ. “It should be stressed that too great a deterioration of intellectual skills progressively leads to a very problematic psychosocial dependence. Here, we could succeed in protecting this population”, notes Stéphan Eliez.

Once the results of this study  are confirmed, the effect of SSRIs could be tested on other types of patients and possibly prescribed preventively to  people at risk of intellectual deterioration, such as individuals with other genetic syndromes like Fragile X or Down’s syndrome, or children of schizophrenic parents. “We also want to investigate whether the 3% to 4% of adolescents in the general population who develop psychotic symptoms would see this risk reduced by taking this drug”, continues Valentina Mancini.

The Geneva team will now compare the results obtained from their research cohort with international databases in order to confirm the neuroprotective role induced by these treatments prescribed at the end of childhood, adolescence being the critical phase for the onset of psychotic diseases.

Featured image: The frontal lobe and hippocampus (purple) are among the areas most affected by impairment due to psychotic illness. Treatment with selective serotonin reuptake inhibitors seems to have a neuroprotective effect on the maturation of these regions. © UNIGE

Reference: Mancini, V., Maeder, J., Bortolin, K. et al. Long-term effects of early treatment with SSRIs on cognition and brain development in individuals with 22q11.2 deletion syndrome. Transl Psychiatry 11, 336 (2021).

Provided by University of Geneve

Replicating Patients Tumours To Test Different Treatments (Medicine)

UNIGE Researchers have developed in vitro tumour models that incorporate components of the tumour and elements of the patient’s immune system to test the effectiveness of treatments.

Every tumour is different, every patient is different. So how do we know which treatment will work best for the patient and eradicate the cancer? In order to offer a personalised treatment that best suits the case being treated, a team of scientists led by the University of Geneva (UNIGE), Switzerland, had already developed a spheroidal reproduction of tumours that integrates the tumour cells, but also their microenvironment. However, the immune system had not yet been taken into account, even though it can either be strengthened or destroyed by the treatment given to the patient. Today, the Geneva team has succeeded in integrating two types of immune cells that come directly from the patient into the spheroidal structure, making it possible to test the various possible treatments and select the most effective. These results can be read in the journal Cancers.

In order to test cancer treatments, scientists use 2D cultures of cancer cells. However, these are only an artificial system, as they do not represent the 3D tumour in all its complexity. This is why the team of Patrycja Nowak-Sliwinska, professor at the Section of Pharmaceutical Sciences of the Faculty of Science of the UNIGE, has developed a spheroidal structure that reproduces the microenvironment of the tumour. “The idea is to create a 3D structure from the cells of the tumour, while also integrating the fibroblasts –  cells that make up the mass of the tumour –  and the endothelial cells, which allow the tumour to feed and be vascularised.” This method, which has since been used by the University Hospitals of Geneva (HUG), allows us to get closer to the tumour as it is present in the patient’s body. “However, an important factor was still missing: the cells of the immune system”, explains the Geneva researcher.

The critical role of the immune system in the fight against cancer

The immune system is the primary fighter against tumours and it reacts differently depending on the treatment prescribed to the patient: its effectiveness can either be increased or decreased. Today, the Geneva team, in collaboration with the universities of Lausanne and Amsterdam, has succeeded in integrating two types of immune cells into its spheroidal structure: macrophages and T lymphocytes. “This technological advance makes it possible to test the effects of a treatment not only on the tumour, but also on the immune system!”, enthuses Magdalena Rausch, researcher at the UNIGE’s Section of Pharmaceutical Sciences and first author of the study. To do this, the scientists first take cells from the patient’s tumour to recreate it in vitro in the form of a spheroidal structure, and then they isolate the immune cells and inject them into the 3D structure. “Once this step has been completed, which takes 24 hours, we can test the various possible treatments for this cancer on our reproduction of the tumour and study which one will be most suitable for the patient, taking into account the effects on the tumour cells, but also on the immune system”, explains Patrycja Nowak-Sliwinska.

This technique, which is relatively inexpensive and fast, would make it possible to propose a personalised treatment for each patient, while offering an effective alternative to several animal experimentations. “This platform opens up many possibilities for testing drug combinations, taking into account the different types of cancer, their mutations and the immune reactions specific to each person treated”, concludes Patrycja Nowak-Sliwinska.

Featured image: The spheroid includes cancer cells, endothelial cells, fibroblasts, monocytes and human T cells. Fluorescently labelled immune cells (green, monocytes; red, T cells) can infiltrate the preformed spheroid within 12 hours. Scale bar = 100 µm. © Magdalena Rausch

Reference: Rausch, Magdalena; Blanc, Léa; De Souza Silva, Olga; Dormond, Olivier; Griffioen, Arjan W.; Nowak-Sliwinska, Patrycja. 2021. “Characterization of Renal Cell Carcinoma Heterotypic 3D Co-Cultures with Immune Cell Subsets” Cancers 13, no. 11: 2551.

Provided by University of Geneve

Bilingualism As A Natural Therapy For Autistic Children (Language)

An international team led by UNIGE demonstrates that the characteristics of bilingualism allow autistic children to compensate for certain fundamental deficits.

Affecting more than one in a hundred children, autism spectrum disorder is one of the most common neurodevelopmental disorders. It has a particular impact on social interaction, including difficulties in understanding other people’s perspectives, beliefs, desires and emotions, known as ‘theory of mind’. Bilingual families with an autistic child often tend – and are sometimes encouraged – to forego the use of one of the home languages, so as not to further complicate the development of their child’s communicative skills. A researcher from the University of Geneva (UNIGE, Switzerland), in collaboration with the Universities of Thessaly (Greece) and Cambridge (Great-Britain), has shown that bilingualism allows autistic children to partially compensate for deficits in theory of mind and executive functions, which are at the root of many of their challenges. These results can be read in the journal Autism Research.

Diagnosed in early childhood, autism spectrum disorder has a particular impact on a child’s social and communicative abilities. “It is a spectrum, which is why the intensity of the symptoms varies greatly”, explains Stéphanie Durrleman, a researcher in the Department of Linguistics at the UNIGE Faculty of Arts and co-author of the study. “But what children with autism have in common is that they have difficulties putting themselves in the place of their interlocutor, focusing on the latter’s point of view and thus disengaging their attention from their own perspective.” Autism therefore affects not only everything that has to do with the theory of mind – understanding the beliefs, emotions, intentions and desires of others – but also often executive functions, including attentional abilities.

Could benefits of bilingualism be applied to children with autism?

Studies on bilingualism have shown that children without autism who use several languages have increased theory of mind and executive function skills compared to monolingual children. “Bilingualism therefore seems to bring benefits precisely where the autistic child has difficulties”, says Stéphanie Durrleman. “We therefore wondered whether bilingual autistic children manage to mitigate the difficulties of their neurodevelopmental disorder by using two languages every day.”

To test this hypothesis, the researchers from the universities of Geneva, Thessaly and Cambridge followed 103 autistic children aged 6 to 15, 43 of whom were bilingual. “In order to observe the real effects of bilingualism on their socio-communicative skills, we grouped them according to their age, gender and the intensity of their autistic disorder”, explains Eleni Peristeri, researcher at the Faculty of Medicine of the University of Thessaly and co-author of the study. The participants then performed various tasks to assess their theory of mind and executive function skills. The bilinguals quickly distinguished themselves by scoring higher than their monolingual peers. “On tasks relating to theory of mind, i.e. their ability to understand another person’s behaviour by putting themselves in their place, the bilingual children gave 76% correct answers, compared with 57% for the monolingual children”, notes the Greek researcher. The same is true for executive functions: the score for correct responses in bilinguals is twice that of monolinguals. But why are the differences so clear?

“Bilingualism requires the child to work first on skills directly related to theory of mind, i.e. he or she must constantly be concerned with the knowledge of others: Does the person I am speaking to speak Greek or Albanian? In what language should I talk to him or her? Then, in a second phase, the child uses his executive functions by focusing his attention on one language, while inhibiting the second”, explains Eleni Peristeri. This is a real gymnastics for the brain, which acts precisely on the deficits linked to the autistic disorder.

Encouraging bilingualism instead of giving it up

“From our evaluations, we can clearly see that bilingualism is very beneficial for children with autism spectrum disorders”, enthuses Stéphanie Durrleman. In order to certify that the socio-economic level in which the participants grew up did not play a role in the results, this was also recorded and it turned out that the bilingual children were mostly in a lower socio-economic environment than the monolinguals. “We can therefore affirm that benefits in theory of mind and executive functions emerge in bilinguals, even when there is a socio-economic disadvantage”, says the Geneva researcher.

These findings are important for the care of children diagnosed with autism. “Indeed, as this neurodevelopmental disorder often affects language acquisition, bilingual families tend to give up the use of one of the two languages, so as not to exacerbate the learning process. However, it is now clear that far from putting autistic children in difficulty bilingualism can, on the contrary, help these children to overcome several aspects of their disorder, serving as a kind of natural therapy”, concludes Stéphanie Durrleman.

Featured image credit: Garner

Reference: Peristeri, E., Baldimtsi, E., Vogelzang, M., Tsimpli, I. M., & Durrleman, S. (2021). The cognitive benefits of bilingualism in autism spectrum disorder: Is theory of mind boosted and by which underlying factors? Autism Research, 1– 15.

Provided by University of Geneve

New Insight Into Early Stages of Bowel Cancer Could Provide an Effective Treatment Strategy (Medicine)

An international team of scientists have identified key factors underpinning the development of bowel or colorectal cancer in patients with a genetic predisposition to the disease.

The study – led by researchers at the Cancer Research UK Beatson Institute at the University of Glasgow and the University of Helsinki, and published today in Nature – provides crucial insight into the early stages of the disease, and also identifies a molecule that’s a ‘key player’ in this process, information which could lead to new ways to prevent tumour development in high-risk individuals.

The study, done in mouse models, looked at APC, one of the most commonly mutated genes in colorectal tumours, to identify how APC mutant cells compete with neighbouring normal cells. The researchers discovered the involvement of a molecule called NOTUM in the development of the disease. They hope that one day it will be possible to deploy NOTUM inhibitors, some of which are currently under development, as a possible early treatment.

Professor Owen Sansom, co-investigator of the Cancer Research UK Grand Challenge SPECIFICANCER team and Director of the Cancer Research UK Beatson Institute, University of Glasgow said: “We’ve known for a few years that APC loss gives cells a competitive advantage over their non-mutant neighbours, making them very good at forming cancer in the gut.”

“With this study, we’ve used model systems to uncover what causes APC-mutant cells to become super-competitors and drive the very early stages of colorectal cancer.”

The researchers believe that pinpointing the involvement of the molecule NOTUM in these early stages of colorectal cancer could be the key to preventing the disease in high-risk individuals, such as those with Familial Adenomatous Polyposis (FAP), who inherit a defective copy of APC.

Dustin Flanagan, co-lead on the study, said: “Rather than targeting the APC-mutant cells, our strategy has been to bolster the fitness of the surrounding normal cells by inhibiting NOTUM.

“By removing the suppressive effect NOTUM has on neighbouring cells, Apc-mutants lose their competitive edge and it becomes a fairer fight, slowing or even preventing tumour growth.”

The study is the result of a collaboration with colleagues at the Alzheimer’s Research UK Drug Discovery Institute at University College London.

Prof Sansom added: “Our team’s findings feed into our wider goal – to better understand why certain mutations drive cancer in specific tissues and not others, so as to develop novel preventative and treatment approaches.

“The next steps would be to test our NOTUM inhibitors on other forms of cancer driven by mutations that behave similar to APC, such as liver and stomach cancer. We’re also keen to trial the NOTUM inhibitor on advanced models of CRC and look at the effects on late-stage disease progression such as metastasis and remodelling of the tumour microenvironment.”

The study, ‘NOTUM from Apc-mutant cells biases clonal competition to initiate cancer’, is published in Nature and funded by Cancer Research UK.

Provided by University of Glasgow

Very High Use Of Antibiotics In COVID-19 Treatment Could Be Reduced (Medicine)

The very high use of antibiotics in patients hospitalised with COVID-19 is often not necessary, and risks worsening global antimicrobial resistance.

New research led by the University of Glasgow as part of the ISARIC (International Severe Acute Respiratory and emerging Infections Consortium) WHO Clinical Characterisation Protocol UK (CCP-UK), found that antibiotic use was very high in hospitalised COVID-19 patients in the UK during the first wave despite confirmed bacterial infection being uncommon.

The study, which is published in The Lancet Microbe and was conducted in collaboration with the Universities of Edinburgh and Liverpool and Imperial College London, found that overall 85% of COVID-19 patients received one or more antibiotics during their hospital admission, with the highest use in critical care, while 37% of patients were prescribed antibiotics prior to admission.

There was high use of broad-spectrum antibiotics – those active against a very wide range of bacteria – and evidence that this could be reduced by using more targeted but equally appropriate alternatives. Importantly, confirmed bacterial infections in people with COVID-19 were uncommon, especially when first admitted to hospital, so a more restrictive approach to using antibiotics would be safe and should be encouraged. Most of the bacteria identified represented secondary infections which began more than 48 hours from admission.

Researchers also found that secondary infections occurring after hospitalisation were not specific to COVID-19 infection and more in keeping with hospital-associated infections and particularly those infections typically seen in intensive care units. These findings will help to inform most appropriate approach to antibiotic prescribing in patients with COVID-19 suspected of having a bacterial infection.

Although co-infections were rarely observed during the first wave of the pandemic there remains a need to monitor hospitalised patients in light of increased use of steroids and other COVID-19 treatments, which may increase susceptibility to bacterial infection. However, the researchers argue that over-prescription of antibiotics and particularly broad-spectrum antibiotics in the majority of hospitalised patients with COVID-19 raises significant concern regarding the potential detrimental impact on antimicrobial resistance globally. The importance of efforts to safely reduce and control antibiotic prescribing in COVID-19 should not be underestimated.

Dr Antonia Ho, lead author of the study from the MRC-University of Glasgow Centre for Virus Research, said: “Until now, a detailed understanding of the nature of bacterial co-infections identified in patients with COVID-19, and the frequency and types of antibiotics these patients have been prescribed has been lacking. This study demonstrates the very high antibiotic use we see in hospitalised COVID-19 patients may not be necessary, indeed it may contribute to antimicrobial resistance.

“While some COVID-19 patients will require antibiotics, mostly for secondary infections which develop after admission to hospital, our data shows that not all COVID-19 patients should be prescribed antibiotics. The longer someone is in hospital, particularly if they are in critical care, the more vulnerable they are to develop secondary infections, and these should continue to be monitored. However, the bugs we identified are similar to those found in patients with hospital-acquired infection, and not specific to COVID-19.”

Dr. Clark Russell, a Clinical Lecturer at the University of Edinburgh said: “Bacterial chest and bloodstream infections are uncommon complications of COVID-19. This work identifies which bacteria tend to cause these infections when they do occur, helping clinicians to make a more informed choice about the best antibiotics to give people when needed.”

Prof Calum Semple, Co-Lead of the study said, “We only have safe surgery and medical cures for many life threatening conditions because antibiotics were discovered and mostly still work.  Overuse of antibiotics needs to be avoided to prevent emergence of resistance.  When the current threat from COVID-19 subsides, the problem of antimicrobial resistance will remain a threat.”

Bacterial co-infections and secondary infections are commonly identified in severe influenza (up to a quarter of cases) and other severe respiratory viral infections, where they are also associated with increased morbidity and mortality. Current national and international COVID-19 guidelines vary in their recommendations on non-targeted antibiotic use. UK guidelines advise against antibiotic use when the respiratory tract infection is thought to be due to COVID-19, without specific evidence of bacterial infection.

The paper ‘Co-infections, secondary infections, and antimicrobial usage in hospitalised patients with COVID-19 during the first wave from the ISARIC WHO CCP-UK study: a prospective, multicentre cohort study’ is published in the Lancet Microbe. The work was funded by The Medical Research Council (MRC), National Institute for Health Research (NIHR) and by the NIHR Health Protection Research Unit (HPRU), Wellcome, and the Bill and Melinda Gates Foundation.

Provided by University of Glasgow

Study Shows Novel Test Can Detect New and Recurrent Bladder Cancer (Medicine)

A revolutionary new urine screening test that utilizes a novel Keratin 17 (K17) cancer biomarker can detect the presence of new bladder cancer in patients with hematuria, or blood in the urine, according to a study led by researchers at Yale Cancer Center, Stony Brook University, and KDx Diagnostics, Inc. The findings also show the test can detect recurrent bladder cancer in patients under surveillance for relapse.

The study was published online June 4 in American Journal of Clinical Pathology.

According to the American Cancer Society, an estimated 81,000 cases of bladder cancer will be diagnosed in the United States this year. However, accurate detection of bladder cancer, or urothelial carcinoma (UC), is often difficult and expensive, requiring invasive camera-based testing methodology.

“Current methods used in cytology labs are based on subjective microscopic features that may not reliably distinguish between benign cells and low-grade urothelial carcinomas,” said Luisa Escobar-Hoyos, assistant professor of therapeutic radiology at Yale Cancer Center and co-lead author of the study. “There was an unmet clinical need to find biomarkers to improve diagnostic accuracy for UC. Following up on prior studies from our lab, this research confirms that K17 is a highly sensitive diagnostic test for initial screening and detection of recurrent cancer across all grades of UC.”

The study was defined by two matched cohorts: a discovery cohort in which the optimal number of positive cells for optimal sensitivity and specificity was identified, and a validation cohort in which a new set of patients was evaluated. In this validation cohort, the sensitivity and specificity in patients were 86% and 92%, respectively. When the patients were divided into hematuria and recurrent bladder cancer populations, the data showed sensitivity and specificity of 100% and 83%, respectively, in patients with hematuria, and sensitivity and specificity of 92% and 100%, respectively, in patients with recurrent bladder cancer.

“We are pleased to report that the test using a K17 biomarker continues to show high sensitivity in identifying both new cancers from hematuria patients and recurrent cancer from patients being monitored for UC,” said Nam W. Kim, PhD, chief executive officer and chief technology officer of KDx Diagnostics, Inc. “There is now a growing body of evidence that the non-invasive, K17 urine test will make a significant positive impact on detection and management of UC.”

Featured image: Brown staining of the Keratin 17 biomarker can be seen in malignant cells within a cluster of bladder cells (dark blue). The large, pale blue cells are normal cells from another tissue secreted in urine. © Yale University

Reference: Sruthi Babu, MD, PhD, Nam W Kim, PhD, Maoxin Wu, MD, PhD, Ina Chan, Luisa F Escobar-Hoyos, PhD, Kenneth R Shroyer, MD, PhD, Keratin 17 Is a Novel Cytologic Biomarker for Urothelial Carcinoma Diagnosis, American Journal of Clinical Pathology, 2021;, aqab050,

Provided by Yale University