Positive media coverage of cannabis studies regardless of therapeutic effect

Photo Credit: Julia Teichmann

In cannabis trials against pain, people who take placebos report feeling largely the same level of pain relief as those who consume the active cannabinoid substance. Still, these studies receive significant media coverage regardless of the clinical outcome, report researchers from Karolinska Institutet in Sweden in a study published in JAMA Network Open.

“We see that cannabis studies are often described in positive terms in the media regardless of their results,” says the study’s first author Filip Gedin, postdoc researcher at the Department of Clinical Neuroscience, Karolinska Institutet. “This is problematic and can influence expectations when it comes to the effects of cannabis therapy on pain. The greater the benefit a treatment is assumed to have, the more potential harms can be tolerated.”

The study is based on an analysis of published clinical studies in which cannabis has been compared with placebo for the treatment of clinical pain. The change in pain intensity before and after treatment were the study’s primary outcome measurement.

The analysis drew on 20 studies published up to September 2021 involving almost 1,500 individuals.

Protein Spheres Protect the Genome of Cancer Cells

MYC proteins are colored green in this figure. In normally growing cells, they are homogeneously distributed in the cell nucleus (left). In diverse stress situations, as they occur in cancer cells, they rearrange themselves, form sphere-like structures and thus surround particularly vulnerable sections of the genome.
Image Credit: Team Martin Eilers / Universität Würzburg

Hollow spheres made of MYC proteins open new doors in cancer research. Würzburg scientists have discovered them and report about this breakthrough in the journal "Nature".

MYC genes and their proteins play a central role in the emergence and development of almost all cancers. They drive uncontrolled growth and altered metabolism of tumor cells. And they help tumors hide from the immune system.

MYC proteins also show an activity that was previously unknown – and which is now opening new doors for cancer research: They form hollow spheres that protect particularly sensitive parts of the genome. If these MYC spheres are destroyed, cancer cells will die.

This was reported by a research team led by Martin Eilers and Elmar Wolf from the Institute of Biochemistry and Molecular Biology at Julius-Maximilians-Universität Würzburg (JMU, Bavaria, Germany) in the journal Nature. The researchers are convinced that their discovery is a game changer for cancer research, an important breakthrough on the way to new therapeutic strategies.

Major discovery about mammalian brains surprises researchers

Illustration shows vacuolar-type adenosine triphosphatases (V-ATPases, large blue structures) on a synaptic vesicle from a nerve cell in the mammalian brain.
Illustration Image: C. Kutzner, H. Grubmüller and R. Jahn/Max Planck Institute for Multidisciplinary Sciences.

Major discovery about mammalian brains surprises researchers, University of Copenhagen researchers have made an incredible discovery. Namely, a vital enzyme that enables brain signals is switching on/off at random, even taking hours-long “breaks from work”. These findings may have a major impact on our understanding of the brain and the development of pharmaceuticals. 

Millions of neurons are constantly messaging each other to shape thoughts and memories and let us move our bodies at will. When two neurons meet to exchange a message, neurotransmitters are transported from one neuron to another with the aid of a unique enzyme.

This process is crucial for neuronal communication and the survival of all complex organisms. Until now, researchers worldwide thought that these enzymes were active at all times to convey essential signals continuously. But this is far from the case.

Using a groundbreaking method, researchers from the University of Copenhagen’s Department of Chemistry have closely studied the enzyme and discovered that its activity is switching on and off at random intervals, which contradicts our previous understanding.

Covid-19: the Spike protein is no longer the only target

Possible mechanism of action of a drug targeting Nsp1 of SARS-CoV-2. In infected cells, Nsp1 blocks the ribosome mRNA canal by acting as a "cap" that prevents the expression of the host's mRNA. Linking a ligand to the proposed cryptic pocket highlighted in purple could prevent blockage mediated by Nsp1 and, ultimately, restore the ability of the ribosome to initiate the translation of the mRNA.
Photo Credit: UNIGE Alberto Borsatto

A research team led by the UNIGE reveals a hidden cavity on a key SARS-CoV-2 protein to which drugs could bind.

With the continuous emergence of new variants and the risk of new strains of the virus, the development of innovative therapies against SARS-CoV-2 remains a major public health challenge. Currently, the proteins that are on the surface of the virus and/or are involved in its replication are the preferred therapeutic targets, like the Spike protein targeted by vaccines. One of them, the non-structural protein Nsp1, had been studied little until now. A team from the University of Geneva (UNIGE), in collaboration with University College London (UCL) and the University of Barcelona, has now revealed the existence of a hidden ''pocket’ on its surface. A potential drug target, this cavity opens the way to the development of new treatments against Covid-19 and other coronaviruses. These results can be found in the journal eLife.

Probiotic ‘backpacks’ show promise for treating inflammatory bowel diseases

Probiotic bacteria (teal) coated in a layer of biomaterial as they travel through a human intestine. Attached to the bacteria are reactive oxygen species nano-scavengers.
Image Credit: Quanyin Hu

Like elite firefighters headed into the wilderness to combat an uncontrolled blaze, probiotic bacteria do a better job quelling gut inflammation when they’re equipped with the best gear.

A new study by researchers at the University of Wisconsin–Madison demonstrates just how much promise some well-equipped gut-friendly bacteria hold for improving treatments of inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis.

Led by Quanyin Hu, a biomedical engineer and professor in the UW–Madison School of Pharmacy, the research builds on technology the team had previously designed. That prior technology encases beneficial bacteria within a very thin protective shell to help them survive an onslaught of stomach acids and competing microbes long enough to establish and multiply in the guts of mice.

While the technology makes orally administered probiotics more effective, IBD is a complex disease that usually involves more than gut microbial communities that are out of whack.

“IBD is a complicated disease, and you need to attack it at different angles,” says Hu.

So, Hu and his colleagues devised specialized nanoparticles to neutralize molecules implicated in IBD. They’ve also figured out a way of attaching these nanoparticle “backpacks” to beneficial bacteria after encasing them in the protective coating.

Injections for diabetes, cancer could become unnecessary

Young woman injecting insulin
Photo Credit: Pavel Danilyuk

Researchers at UC Riverside are paving the way for diabetes and cancer patients to forget needles and injections, and instead take pills to manage their conditions.

Some drugs for these diseases dissolve in water, so transporting them through the intestines, which receive what we drink and eat, is not feasible. As a result, these drugs cannot be administered by mouth. However, UCR scientists have created a chemical “tag” that can be added to these drugs, allowing them to enter blood circulation via the intestines.

The details of how they found the tag, and demonstrations of its effectiveness, are described in a new Journal of the American Chemical Society paper.

The tag is composed of a small peptide, which is like a protein fragment. “Because they are relatively small molecules, you can chemically attach them to drugs, or other molecules of interest, and use them to deliver those drugs orally,” said Min Xue, UCR chemistry professor who led the research.

Xue’s laboratory was testing something unrelated when the researchers observed these peptides making their way into cells.

Efficient mRNA delivery by branched lipids

A cross-section of an LNP-RNA. The mRNA (red) is encapsulated by lipids (blue spheres with tails.
 Image Credit: Yusuke Sato

A novel branched lipid that has a high stability in storage and a high efficiency in the delivery of mRNA to cells has been developed.

Messenger RNA (mRNA) are biological molecules that transfer the information coded by genes in the nucleus to the cytoplasm for protein synthesis by ribosomes. mRNA sequences can be designed to encode specific proteins; the most well-known example of this are the mRNA vaccines for COVID-19. mRNA molecules are large and chemically unstable, so a vector must be utilized to deliver mRNA to the cells. One of the most advanced technologies for the delivery of mRNA are lipid nanoparticles (LNPs), which are composed of ionizable lipids, cholesterol, helper lipids and polyethylene glycol.

A team of researchers led by Assistant Professor Yusuke Sato and Professor Hideyoshi Harashima at the Faculty of Pharmaceutical Sciences, Hokkaido University, and by Kazuki Hashiba at the Nitto Denko Corporation have developed a novel branched ionizable lipid which, when included in LNPs, greatly increases the efficiency of mRNA delivery. Their results were published in the journal Small Science.

How Pathogens Hijack Immune System to Cause Vaccine-Enhanced Disease

Associate Professor Steven Szczepanek (standing, left) with graduate students Tyler Gavitt (seated) and Arlind Mara (standing, right).
Photo Credit: Jason Sheldon/UConn

Researchers in the College of Agriculture, Health and Natural Resources are working to unlock a decades-long mystery that has hampered development of a walking pneumonia vaccine.

Associate Professor Steven Szczepanek and Professor Steven Geary from the Department of Pathobiology and Veterinary Science, along with former graduate students Tyler Gavitt and Arland Mara, published findings that help explain how Mycoplasma pneumoniae (Mp) hijacks our immune system following vaccination.

They shared their findings in two recent publications in Nature journal npj Vaccines.

Mp is a common pathogen that causes walking pneumonia. While this respiratory infection is not typically severe, it is a common co-pathogen with illnesses that spread in the same way, like the flu or COVID-19, which can cause more severe illnesses, especially in older or immunocompromised adults.

In the 1960s, scientists began working to develop an Mp vaccine. They killed the bacteria and injected it into human subjects, thinking it would provide protection from actual infection. But that’s not what happened.

A new nanoparticle to act at the heart of cells

This electron micrograph documents the porous nature of silica nanoparticles. These pores are large enough to allow entrance of a large number of NSA molecules. Here, they are protected until being taken up by the immune cells. At this point NSA is released and can stop the inflammatory processes.
Credit: UNIGE - Carole Bourquin

How can a drug be delivered exactly where it is needed, while limiting the risk of side effects? The use of nanoparticles to encapsulate a drug to protect it and the body until it reaches its point of action is being increasingly studied. However, this requires identifying the right nanoparticle for each drug according to a series of precise parameters. A team from the University of Geneva (UNIGE) and the Ludwig Maximilians Universität München (LMU) has succeeded in developing a fully biodegradable nanoparticle capable of delivering a new anti-inflammatory drug directly into macrophages - the cells where uncontrolled inflammatory reactions are triggered - ensuring its effectiveness. In addition, the scientists used an invitro screening methodology, thus limiting the need for animal testing. These results, recently published in the Journal of Controlled Release, open the way to an extremely powerful and targeted anti-inflammatory treatment.

Inflammation is an essential physiological response of the body to defend itself against pathogens such as bacteria. It can, however, become problematic when it turns into a chronic condition, such as in cancers, autoimmune diseases or certain viral infections. Many treatments already exist, but their action is often not very targeted, high doses are required and deleterious side effects are frequent. Macrophages, large immune cells whose natural function is to absorb pathogens and trigger inflammation to destroy them, are often involved in inflammatory diseases. When overactivated, they trigger an excessive inflammatory response that turns against the body instead of protecting it.

New experimental treatment can stop the growth of schwannoma tumors

Researchers showed that after just 21 days of the drugs being administered, tumor growth can be strongly and significantly reduced.
Photo Credit: MART PRODUCTION

Two novel and orally administered drugs can not only block the growth, but also shrink the size, of a tumor type found in the nervous system, new research has shown.

The tumors, schwannomas, most frequently grow on the nerves that bring hearing and balance information into the brain. Schwannomas are the most common nerve sheath tumor, and can occur in anyone but are also linked to a hereditary condition known as Neurofibromatosis Type II (NF2).

In NF2, where the function of the protein Merlin is lost in cells, patients frequently develop not only schwannomas, but also meningioma tumors associated with the brain and spinal cord.

The treatment of both tumor types is difficult, with surgery being the current mainstay but also carrying a high risk of damage to the surrounding normal nervous system tissue.

With an urgent need for new treatments, an international team of scientists focused on the Hippo signaling pathway, which normally controls organ size in human tissues and cells, but is dysregulated in multiple types of cancer.

Therapeutic HIV vaccine with Oxford technology achieves encouraging results

Artist illustration of the HIV virus.
Illustration Credit: Darwin Laganzon

A phase I/IIa clinical trial that the University of Oxford collaborated on has demonstrated that a T-cell therapeutic HIV vaccine was associated with better control of the virus rebound when antiretroviral therapy (ART) was temporarily withdrawn.

Researchers carrying out the AELIX-002 study, whose results have been published in Nature Medicine, reported that two fifths of participants without any genetic background associated with spontaneous HIV control were able to stay off ART for the six-month duration of the supervised ART pause.

The vaccine in the study – developed by AELIX Therapeutics – delivered the HIVACAT T-cell Immunogen (HTI) using a combination of DNA vector, modified vaccinia virus Ankara (MVA) vector and simian adenovirus vector ChAdOx1. The latter two vaccines were constructed at Oxford.

Tomáš Hanke, Professor of Vaccine Immunology at the Jenner Institute, Nuffield Department of Medicine, who leads on HIV vaccine development, said:

‘This result provides further encouragement that active immunization against HIV may be possible, slowing HIV replication, providing a window of treatment holidays for people living with HIV and eventually leading to HIV cure. T cells/T-cell vaccines are likely to play an important part in the final package for HIV cure and, perhaps, other advanced therapies for difficult diseases.’

A new weapon against antibiotic-resistant bacteria

This inoculated MacConkey agar culture plate cultivated colonial growth of Gram-negative, small rod-shaped and facultatively anaerobic Klebsiella pneumoniae bacteria. K. pneumoniae bacteria are commonly found in the human gastrointestinal tract, and are often the cause of hospital acquired, or nosocomial infections involving the urinary and pulmonary systems.
Credit: CDC

The unreasonable use of antibiotics has pushed bacteria to develop resistance mechanisms to this type of treatment. This phenomenon, known as antibiotic resistance, is now considered by the WHO as one of the greatest threats to health. The lack of treatment against multi-resistant bacteria could bring us back to a time when millions of people died of pneumonia or salmonella. The bacterium Klebsiella pneumoniae, which is very common in hospitals and particularly virulent, is one of the pathogens against which our weapons are becoming blunt. A team from the University of Geneva (UNIGE) has discovered that edoxudine, an anti-herpes molecule discovered in the 60s, weakens the protective surface of Klebsiella bacteria and makes them easier to eliminate for immune cells. These results can be read in the journal PLOS One.

Klebsiella pneumoniae causes many respiratory, intestinal and urinary tract infections. Due to its resistance to most common antibiotics and its high virulence, some of its strains can be fatal for 40% to 50% of infected people. There is an urgent need to develop new therapeutic molecules to counter it. “Since the 1930s, medicine has relied on antibiotics to get rid of pathogenic bacteria,” explains Pierre Cosson, professor in the Department of Cell Physiology and Metabolism at the UNIGE Faculty of Medicine, who led this research. “But other approaches are possible, among which trying to weaken the bacteria’s defense system so that they can no longer escape the immune system. This avenue seems all the more promising as the virulence of Klebsiella pneumoniae stems largely from its ability to evade attacks from immune cells.”

Bulking Up to Beat Bacteria

The inhibitor-binding site of the wild-type MexB pump. (a) The crystal structure of the inhibitor ABI-PP bound to the MexB trimer. Three MexB monomers are shown in green, blue, and red, representing the access, binding, and extrusion monomer, respectively. ABI-PP is shown as a yellow space-filling model. (b) A close-up view of the inhibitor binding site. The substrate translocation pathway is shown as a solid gray surface. The proximal and distal binding pockets are indicated in green and blue circles, respectively. The inhibitor binding pit is shown as a red surface. The ABI-PP molecule is represented as a yellow stick model. (c) A detailed view of the inhibitor-binding site. Carbon atoms of ABI-PP are indicated in yellow while amino acid residues are indicated in green. The classification of these amino acids is shown on the right side of the panel.
Image Credit: 2022 Yamasaki et al., Spatial Characteristics of the Efflux Pump MexB Determine Inhibitor Binding, Antimicrobial Agents and Chemotherapy

The medical profession is in the midst of losing an arms race. Bacterial antibiotic resistance doesn’t just threaten our ability to treat infection but our ability to carry out any treatment where infection is a risk. This includes a raft of life-saving surgeries ranging from coronary bypass operations to organ transplantation. In fact, the number of new antimicrobials being developed is declining each year. Understanding how bacteria resist the influence of antibiotics is essential to winning this arms race: it is time to make up ground.

In a study published this month in Antimicrobial Agents and Chemotherapy, researchers at Osaka University have produced new insights into the structure of a particular bacterial protein known as an efflux pump. This protein is involved in antibiotic resistance and its structure influences the ability of drugs to target it.

Overcoming resistance to colon cancer treatment

Colorectal cancer cells after treatment with FOLFORIXI chemotherapy for 34 weeks. Cell fibers (in green) and nuclei (in blue).
Credit: UNIGE-Nowak-Sliwinka

Colorectal cancer is one of the most common cancers. Its treatment is mainly based on chemotherapy. However, over time, chemotherapy induces resistance in the majority of patients, who end up being unresponsive to the drugs. As a result, the five-year survival rate for those affected is still low. After succeeding in reproducing this resistance in the laboratory, a team from the University of Geneva (UNIGE) has found a way to overcome it. The team has used an optimized combination of drugs belonging to the class of tyrosine kinase inhibitors, which take different pathways to attack cancer cells than chemotherapy. These results, to be found in the journal Cancers, open up new avenues for overcoming treatment resistance and for developing new therapies that are more targeted than chemotherapy.

Colorectal cancer is the third most diagnosed cancer in the world and second only to lung cancer in terms of mortality. It most often develops from the age of 50 in the terminal part of the colon. It results from a change in the DNA of certain cells present in this organ. These cells become cancerous and proliferate in an uncontrolled manner until they form a primary tumor. As in many cancers, these cells can migrate to other parts of the body and form secondary tumors. This is known as metastatic cancer.

While genetics play a role in the development of the disease, the presence of inflammatory bowel diseases (e.g. Crohn’s disease) and certain dietary habits (alcohol, red meat) are also risk factors. In the case of a primary tumor, treatment is based on surgery and chemotherapy. In the case of secondary tumors, it is based on a combination of chemotherapies. These treatments are non-targeted and aggressive. They cause significant side effects. They also lead to progressive resistance to treatment in the majority of patients.

Sand serves up a possible cure for obesity

Engineered particles of purified sand could be the next anti-obesity therapy as new research from the University of South Australia published in journal MPDI Pharmaceutics shows that porous silica can prevent fats and carbohydrates from being adsorbed in the body.

The engineered silica particles are made from purified sand and are optimally designed with a high surface area that enables them to soak up large amounts of digestive enzymes, fats, and sugars within the gastrointestinal tract.

Funded by the Channel 7 Children’s Research Foundation, the study is the first to validate how porous silica particles can impede digestive processes and stop fat and sugar adsorption.

Developed in partnership with Glantreo Limited, the new silica-based therapy will be gentler on the stomach with fewer of the unpleasant side effects associated with the mainstream anti-obesity drug, Orlistat.

Lead researcher, UniSA’s Dr Paul Joyce says this breakthrough finding could change the health outcomes for billions of people struggling with obesity.

A revolutionary method to observe cell transport

Nanobodies (grey) with magnetic probes (red stars) target the desired membrane protein.
Credit: Bordignon, Enrica

Membrane proteins are key targets for many drugs. They are located between the outside and inside of our cells. Some of them, called ‘‘transporters’’, move certain substances in and out of the cellular environment. Yet, extracting and storing them for observation is particularly complex. A team from the University of Geneva (UNIGE), in collaboration with the University of Zurich (UZH), has developed an innovative method to study their structure in their native environment: the cell. The technique is based on electron spin resonance spectroscopy. These results, just published in the journal Science Advances, may facilitate future development of new drugs.

In living organisms, each cell is surrounded by a cell membrane (or ‘‘cytoplasmic membrane’’). This membrane consists of a double layer of lipids. It separates the contents of the cell from its direct environment and regulates the substances that can enter or leave the cell. The proteins attached to this membrane are called ‘‘membrane proteins’’.

Located at the interface between the outside and inside of the cell, they carry various substances across the membrane - into or out of the cell - and play a crucial role in cell signaling, i.e. in the communication system of cells that allows them to coordinate their metabolic processes, development and organization. As a result, membrane proteins represent more than 60% of current drug targets.

Study Finds No Benefit to Taking Fluvoxamine for COVID-19 Symptoms

A study led by the Duke Clinical Research Institute (DCRI) in partnership with Vanderbilt University found no symptomatic or clinical benefit to taking the antidepressant fluvoxamine 50 mg twice daily for 10 days for the treatment of mild-to-moderate COVID-19 symptoms.

“There was no evidence of improvement in time to recovery in participants who took this dose of fluvoxamine versus those who took a placebo,” said Adrian Hernandez, M.D., the study’s administrative principal investigator and executive director of the DCRI.

Findings appear on medRxiv, a pre-publication server, and have been submitted to a peer-reviewed journal.

Researchers looked at the rate of sustained recovery, defined as three days without symptoms, in ACTIV-6. While 75% of participants were still reporting symptoms on day 7, the majority (82%) of these participants reported no limitation in activities.

Covid-19 is linked to increased degradation of connections between nerve cells in a new brain model

Postdoctoral fellow Samudyata and doctoral student Susmita Malwade.
Source: Karolinska Institutet

Researchers at Karolinska Institutet have used cellular reprogramming in a new study to create human three-dimensional brain models and infected them with SARS-CoV-2. In infected models, the brain's immune cells showed an excessive elimination of connections between the nerve cells. The gene expression of these cells also mimicked changes observed in neurodegenerative diseases. The results hope to identify new treatments for cognitive symptoms after Covid-19 infection.

Several studies have reported persistent cognitive symptoms following a covid-19 infection, but the underlying mechanisms for this are still unknown. The researchers behind the study, published in the journal Molecular Psychiatry, have created from human induced pluripotent stem cells (iPS) three-dimensional models of the brain in test tubes, so-called brain organoids. The model differs from previous organoid models in that they also contain microglia - the brain's immune cells. In the infected models, microglia regulated genes involved in phagocytosis, "cell-eating," the researchers could also see how microglia contained an increased amount of proteins from brain cell connections, so-called synapses. The developed model and results of the study can help guide future efforts to address cognitive symptoms in the aftermath of COVID-19 and other neuroinvasive viral infections.

Ural Scientists Developed a Drug to Combat Post-Covidal Complications

According to the scientists, the university and the Ural Branch of the Russian Academy of Sciences are developing world-class materials.
Photo credit: TASS-Ural Press Center, Vladislav Burnashev

Scientists from the Ural Federal University and the Postovsky Institute of Organic Synthesis have developed a drug to combat post-covidal complications, namely, the formation of blood clots. The drug blocks the release of clot-forming compounds caused by coronavirus infection. As the scientists point out, this is a world-class achievement, as new classes of compounds capable of combating the effects of coronavirus have been discovered. Representatives of the Ural Branch of the Russian Academy of Sciences talked about this, as well as about other developments aimed at ensuring the scientific and technological sovereignty of Russia, at a press conference at TASS.

"We develop unique things. This is important to note, because now the concept of import substitution is pushed to the background, and we are talking about the scientific and technological sovereignty of the country. The fact is that import substitution implies reproduction, copying of foreign technologies. We are catching up beforehand. Scientific and technological sovereignty implies independence from external conditions and supremacy in the development of industrial samples and new materials which are superior to foreign analogues in their characteristics. Therefore, it is certain that the Ural scientists successfully solve the task of ensuring scientific and technological progress," emphasizes Victor Rudenko, Academician and Chairman of the Ural Branch of the Russian Academy of Sciences.

Scientists develop a new kind of printable, wearable insect repellent

This is what the ring looks like that could help repel insects.
Photo credit: Uni Halle / Fanfan Du

A new type of insect-repellent delivery device has been developed by scientists from the Martin Luther University Halle-Wittenberg (MLU). With the help of a 3D printer, the active ingredient is first "encapsulated" and formed into the desired shape, such as a ring, which can then be worn and releases an agent designed to repel mosquitoes for a long time. The team has presented its work in the "International Journal of Pharmaceutics".

The researchers have developed their prototypes using "IR3535", an insect repellent developed by MERCK. "Mosquito sprays containing IR3535 are very gentle on the skin and have been used all over the world for many years. That’s why we’ve been using the agent for our experiments", says Professor René Androsch from the MLU. It is usually applied as a spray or lotion and offers several hours of protection. However, Androsch and his team are looking for ways to release the agent over a much longer period, such as by encapsulating it in a wearable ring or bracelet.