Publisher Health

Imperial researchers have discovered a hidden mechanism within hair follicles that allow us to feel touch.
Previously, touch was thought to be detected only by nerve endings present within the skin and surrounding hair follicles. This new research from Imperial College London has found that that cells within hair follicles — the structures that surround the hair fibre — are also able to detect the sensation in cell cultures.
The researchers also found that these hair follicle cells release the neurotransmitters histamine and serotonin in response to touch — findings that might help us in future to understand histamine’s role in inflammatory skin diseases like eczema.
Lead author of the paper Dr Claire Higgins, from Imperial’s Department of Bioengineering, said: “This is a surprising finding as we don’t yet know why hair follicle cells have this role in processing light touch. Since the follicle contains many sensory nerve endings, we now want to determine if the hair follicle is activating specific types of sensory nerves for an unknown but unique mechanism.”
A touchy subject
We feel touch using several mechanisms: sensory nerve endings in the skin detect touch and send signals to the brain; richly innervated hair follicles detect the movement of hair fibres; and sensory nerves known as C-LTMRs, that are only found in hairy skin, process emotional, or ‘feel-good’ touch.
Now, researchers may have uncovered a new process in hair follicles. To carry out the study, the researchers analysed single cell RNA sequencing data of human skin and hair follicles and found that hair follicle cells contained a higher percentage of touch-sensitive receptors than equivalent cells in the skin.

The most lethal feature of any cancer is metastasis, the spread of cancer cells throughout the body. New research led by Penn State reveals for the first time the mechanics behind how breast cancer cells may invade healthy tissues. The discovery, showing that a motor protein called dynein powers the movement of cancer cells in soft tissue models, offers new clinical targets against metastasis and has the potential to fundamentally change how cancer is treated.
“This discovery marks a paradigm shift in many ways,” said Erdem Tabdanov, assistant professor of pharmacology at Penn State and a lead co-corresponding author on the study, recently published in the journal Advanced Science. “Until now, dynein has never been caught in the business of providing the mechanical force for cancer cell motility, which is their ability to move themselves. Now we can see that if you target dynein, you could effectively stop motility of those cells and, therefore, stop metastatic dissemination.”
The project began as a collaboration between Penn State’s Department of Chemical Engineering and Penn State’s College of Medicine, before growing into a multi-institution partnership with researchers at the University of Rochester Medical Center, Georgia Institute of Technology, Emory University, and the U.S. Food and Drug Administration.
The researchers used live microscopy to watch the migration of live breast cancer cells in two different systems modeled after the human body. The first system, a two-dimensional network of collagen fibers, revealed how cancer cells move through an extra cellular matrix that surrounds tumors and showed that dynein was key to the movement of cancer cells. The second system was a three-dimensional model developed by a team led by Amir Sheikhi, Dorothy Foehr Huck and J. Lloyd Huck Early Career Chair in Biomaterials and Regenerative Engineering and assistant professor of chemical engineering and biomedical engineering at Penn State.
The second system was designed to mimic soft tissue using a network of microscopic hydrogel particles or microgels linked together in tumor-like shapes. Like in the two-dimensional model, the researchers found in the three-dimensional model that dynein was “indispensable” in the spread or metastasis of cancer cells.
“Using these three-dimensional models that partially mimic a tumor, we discovered that if we block the dynein, the cancer cells cannot effectively move and infiltrate solid tissues,” Sheikhi said. “In both models, we found that dynein is extremely important for cell locomotion, which suggests a whole new method for cancer management. Instead of killing the cancer cells with radiation or chemotherapy, we are showing how to paralyze them. This is great news because you don’t really have to kill the cells, which is a harsh approach that targets both cancerous and healthy cells. Instead, you just have to stop the cancer cells from moving.”
Tabdanov explained that cell “paralysis” could prove to be an effective treatment strategy for cancer compared to chemotherapeutic treatments, because after surgical removal of the main tumor, it could prevent the cancer from spreading without damaging healthy tissues and cells.

A collaborative study involving researchers from Karolinska Institutet has charted the prevalence of severe physical symptom burden amongst Scandinavians for up to two years after a SARS-CoV-2 infection. Most affected were people who had a severe COVID-19 infection, while the researchers found no elevated prevalence of long COVID in those who had never been bedridden. The study is published in The Lancet Regional Health — Europe.
By mid-October 2023, over 771 million cases of COVID-19 had been reported to the World Health Organization (WHO). An estimated 10 to 20 per cent of the affected have persistent symptoms.
Close to 65,000 participants
In the present study, researchers examined the prevalence of persistent physical symptoms in people with different degrees of COVID-19 severity and compared them with people who had not had a confirmed COVID-19 diagnosis. The study comprised 64,880 adults from Sweden, Denmark, Norway and Iceland with self-reported physical symptoms between April 2020 and August 2022.
Over 22,000 of the participants were diagnosed with COVID-19 during the period, almost 10 per cent of whom were bedridden for at least seven days. The prevalence of chronic symptoms such as shortness of breath, chest pain, dizziness, headaches, and low energy/ fatigue, was 37 per cent higher in those who had had a COVID-19 diagnosis than in those who had not.
Patients who had been bedridden for at least seven days during the SARS-CoV-2 infection had the highest prevalence of severe physical symptom burden, over double that of those not diagnosed with COVID-19. They also had the most persistent symptoms for up to two years after diagnosis.
The symptoms might need longer monitoring
“Long COVID has grown into a major public health problem since a large proportion of the global population has been infected,” says Emily Joyce, doctoral student at the Institute of Environmental Medicine, Karolinska Institutet in Sweden and one of the study’s first authors. “Our results show the long-term health consequences of the pandemic and highlight the importance of monitoring physical symptoms for up to two years after diagnosis, especially in people who experienced severe COVID-19.”

The SARS-CoV-2 virus responsible for COVID-19 can cause severe acute respiratory syndrome, contrasting with other coronaviruses that were known to cause mild seasonal colds prior to its emergence in 2019. This raises the question of why one coronavirus affects humans more severely than another. Scientists at the Institut Pasteur, Université Paris Cité and the VRI have now provided part of the answer by identifying a gateway used by the seasonal coronavirus HKU1 to enter human cells. HKU1 binds to a different receptor than SARS-CoV-2, which may partly explain the difference in severity between these two coronaviruses. Receptors provide a useful means of elucidating coronavirus transmissibility and pathology as part of surveillance work on viral evolution. These results are published in the October 25, 2023 issue of Nature.
Seven coronaviruses are known for their ability to infect humans. Four of these are generally mild: HKU1, 229E, NL63 and OC43, while the other three are more pathogenic: SARS-CoV-1, Mers-CoV and SARS-CoV-2.
The HKU1 virus was first identified in an elderly patient with severe pneumonia in Hong Kong in 2005. Like SARS-CoV-2, HKU1 mainly infects upper respiratory tract cells. However, it rarely affects the bronchi and alveoli in the lungs. The HKU1 virus causes colds and other mild respiratory symptoms. Complications may also occur, including severe respiratory tract infections, particularly in young children, the elderly and immunocompromised individuals. It is estimated that 70% of children are infected before the age of 6. In total, 75 to 95% of the global population has been exposed to HKU1, which is comparable to other seasonal human coronaviruses.
At cellular level, coronavirus spike proteins are cleaved, or split in two, after binding to their receptors. This cleavage phenomenon is vital for viral fusion, entry and multiplication. Some coronaviruses (SARS-CoV-2 and NL63) use the ACE2 receptor as a gateway for entering cells. Until now, HKU1 and OC43 were the only coronaviruses with unknown receptors.
Through collaboration between scientists at eight Institut Pasteur units, it was possible to identify the TMPRSS2 enzyme as the receptor to which HKU1 binds to enter cells. Once binding has occurred, TMPRSS2 triggers fusion of HKU1 with the cell, leading to viral infection. Through a combination of techniques performed in vitro and in cell culture, the scientists demonstrated that the TMPRSS2 receptor has high affinity with the HKU1 spike, which is not the case for SARS-CoV-2.
“Once a receptor has been identified for a virus, it is possible to characterize target cells more accurately, while also gaining insights on viral entry and multiplication mechanisms and infection pathophysiology,” comments, Olivier Schwartz, co-last author of the study and Head of the Institut Pasteur’s Virus and Immunity unit.
“Our findings also shed light on the various evolution strategies employed by coronaviruses, which use TMPRSS2 either to bind to target cells or trigger fusion and viral entry,” adds Julian Buchrieser, co-last author of the study and scientist in the Institut Pasteur’s Virus and Immunity unit.
These human-pathogenic viruses’ use of different receptors probably affects their degree of severity. Receptor levels vary among respiratory tract cells, thus influencing the sensitivity of cells to infection and viral spread. Once the route of viral entry into cells is known, it should also be possible to fight infection more effectively by developing targeted therapies and assess the risk of virulence posed by any future emerging coronaviruses.
In parallel with this work, Institut Pasteur teams led by Pierre Lafaye and Felix Rey have developed and characterized nano-antibodies (very small antibodies) that inhibit HKU1 infection by binding to the TMPRSS2 receptor. These reagents have been patented for potential therapeutic activities.
This work was funded by the above-mentioned research bodies with additional support from the French Foundation for Medical Research (FRM), ANRS-Emerging Infectious Diseases, Vaccine Research Institute, the European HERA DURABLE project, the Labex IBEID and the ANR/FRM Flash Covid project.

Sunscreen usage is climbing, but so are melanoma and skin cancer rates: this, researchers say, is the sunscreen paradox.
“The problem is that people use sunscreen as a ‘permission slip’ to tan,” said Dr. Ivan Litvinov, an Associate Professor in the Department of Medicine and Chair of the Dermatology Division at McGill University and co-author with Dr. Sandra Peláez, Dr. Richie Jeremian and Dr. Pingxing Xie of two recent studies that explore the sunscreen paradox.
“People think they are protected from skin cancer because they are using a product marketed to prevent a condition.”
Most people don’t apply enough sunscreen or stay in the sun for hours after applying sunscreen in the morning. “This gives them a false sense of security,” said Litvinov.
To understand the factors between varying incidence rates of melanoma in the Atlantic provinces of Canada, a group of researchers including Litvinov and Peláez conducted 23 focus groups.
In the study, they found that Canadians living in Nova Scotia and Prince Edward Island — provinces with high melanoma incidence rates — were more likely to report using sun protection, more aware of the health risks of sun exposure, and more apt to follow the UV index. Despite this, they also received more sun exposure due to warmer temperatures and a tendency to engage in outdoor activities.
Similarly, in a second study of the United Kingdom Biobank by Jeremian, Xie and Litvinov, the researchers documented that sunscreen use was surprisingly associated with a more than twofold risk of developing skin cancer.

Proteins are key to all processes in our cells and understanding their functions and regulation is of major importance.
“For many years, we have known that nearly all human proteins are modified by a specific chemical group, but its functional impact has remained undefined,” says professor Thomas Arnesen at the Department of Biomedicine, University of Bergen.
He explains:
“One of the most common protein modifications in human cells is N-terminal acetylation, which is an addition of a small chemical group (acetyl) at the starting tip (N-terminus) of a protein. The modification is launched by a group of enzymes called N-terminal acetyltransferases (NATs).” Despite being “everywhere” in human cells, the functional role of this modification remains mysterious, Arnesen explains.
He is an investigator of a new study that reveals that a core function of this protein modification is to protect proteins from degradation, and this is essential for normal longevity and motility.
CRISPR-Cas9 technology sheds new light on N-terminal acetylation
To address this question, molecular biologist and researcher Sylvia Varland spent two years at the Donnelly Centre for Cellular & Biomolecular Research, University of Toronto, Canada, supported by a FRIPRO mobility grant from the Research Council of Norway.

Six sets of twins who were born conjoined have gathered at Great Ormond Street Hospital (GOSH) in London, where they were treated.The families got together to share stories about their experiences and stories about how they went on to lead healthy lives. The first successful operation separating conjoined twins at GOSH took place in 1985 and since then they have cared for 38 sets of twins.Read more about the twins’ stories here.

A dentist shares five tricks for managing treats.Dr. Apoena Ribeiro is a pediatric dentist and microbiologist at the University of North Carolina at Chapel Hill. She’s also a parent.When her daughter was little and growing up in Brazil, Dr. Ribeiro encouraged her to enjoy a holiday called the Feast of Saints Cosmas and Damian, which involves children collecting large bags of candy. But she also had some strategies for keeping the dental dangers at bay.Here’s what she did back then, and still does today, to protect her family’s oral health on a candy-laden holiday.She minimizes grazing.One sugar-filled night won’t sabotage your oral health, Dr. Ribeiro said — so when her daughter was young, she allowed her to collect and enjoy as much candy as she wanted on sweet-heavy holidays.Once she’d had her fill, Dr. Ribeiro would ask her daughter to sort her candy into two piles: One for her favorites, which she called her “treasures,” and another for the rejects, which they would donate.The “treasures” would be stashed away in a cardboard “treasure box” that could only be opened once or twice a week (though once per day is also OK, Dr. Ribeiro said). When the box was open, her daughter could eat as much candy as she wanted. But once she was done eating and it was closed, she would be cut off from the candy until the box was opened again. Then it was time to brush her teeth.These rules prevented Dr. Ribeiro’s daughter from grazing on candy throughout the day, which could give the cavity-causing bacteria in her mouth more opportunities to feed on sugars and create an environment that could lead to tooth decay. “Free access to the candy is the main problem,” Dr. Ribeiro said.But if the bacteria can only consume the sugar once a day or once every few days, “they will starve,” she said.She times candy eating with meals.The best time to have candy is with or just after a meal, Dr. Ribeiro said. At that point, the bacteria in your mouth may have already filled up on any carbohydrates from the meal, so they’re less able to take advantage of the sugar in the candy. And you produce more saliva when you eat, which helps to rinse the sugar from the candy off your teeth. It also neutralizes acids made by the bacteria that can wear away at your tooth enamel.For most families, having candy with dinner makes the most sense, since all members are likely to be at home and can brush their teeth just after, she said.Giacomo BagnaraShe emphasizes proper brushing right after eating candy.At least twice per day, Dr. Ribeiro brushes her teeth for at least one minute with toothpaste containing fluoride, and she flosses before brushing at night. Two minutes of careful brushing, which is what’s recommended by the American Dental Association, is even better than one, Dr. Ribeiro said.Ideally, Dr. Ribeiro tries to brush her teeth right after she has candy, and always brushes before bedtime.Children should follow the same rules: brushing twice per day — and after they’ve had candy, if possible — and always flossing and brushing before bed.For children under 5 or 6, she said, parents should brush their teeth for them, and parents should supervise the routine until their children are 8 or 9.She takes extra care with the worst candies.Any sticky, gooey or chewy candies that lodge into the grooves and crevices of your teeth can do serious damage. A caramel, for instance, can create a “banquet” for the bacteria in your mouth, Dr. Ribeiro said. And sour candies can increase the risk of damage by making your mouth more acidic, she added.Chocolate is Dr. Ribeiro’s favorite, in part because it’s less likely to linger on teeth. She still enjoys the gooey and chewy candies, but she makes sure to have them with meals, and she brushes and flosses right after to ensure their remnants don’t stick around.She makes Halloween a teachable moment.Dr. Ribeiro knew it would be futile to forbid her daughter from having candy on holidays or at any other time of the year.It’s more helpful to use Halloween as an opportunity to explain to children how sugar from candy or other popular sources like soda or juice can contribute to tooth decay, and how they can protect their teeth while still enjoying special treats, Dr. Ribeiro said.This is knowledge that they’ll carry with them beyond Halloween, she said, adding that good dental habits could improve the health of your teeth in the long run.“This is a concept for life,” she said.

A drug candidate, based on pioneering UCL and Moorfields Eye Hospital research and currently under development by SIFI S.p.A., has been found to be highly effective in treating a rare sight-threatening eye infection in a new international clinical trial.
The findings, published in Ophthalmology, describe the efficacy and safety of the first drug candidate for the treatment of Acanthamoeba keratitis (AK), applying a novel and evidence-based treatment protocol.
AK is one type of microbial keratitis (corneal infection) — a condition that results in inflammation of the cornea (the eye’s clear protective outer layer). AK can cause extreme levels of pain as well as light sensitivity.
AK is relatively uncommon, affecting about one in 37,000 contact lens wearers per year in the UK, but it is responsible for about half the cases of sight loss in this group. Contact lens wearers face an increased risk of the disease; a UCL and Moorfields team recently found that people who wear reusable contact lenses face nearly four times the risk of those wearing daily disposables, while showering with lenses in and wearing lenses overnight also each raised the risk by more than threefold.*
The treatment being studied, low concentration polihexanide (PHMB 0.02%), was first compounded and used in the 1990s to treat AK, introduced by a team co-led by this latest study’s lead author, Professor John Dart, and is widely recommended as a treatment for AK, but it is not a licensed drug, and treatment outcomes have been variable.
Professor John Dart (UCL Institute of Ophthalmology and Moorfields Eye Hospital NHS Foundation Trust) said: “Acanthamoeba keratitis in contact lens users can be prevented by following safe use advice: do use daily disposables if possible, wash and dry hands before handling lenses, maintain good lens and lens case hygiene, and don’tuse them when bathing swimming or showering, or use goggles and renew the lens after use, don’t wear them overnight, and don’t use them every day.
“Unfortunately, when the disease does develop the course is prolonged and, in the recent past, one third of patients have had poor visual outcomes with one quarter requiring surgery at some stage.

Researchers at Nagoya University in Japan created and improved artificial intelligence (AI) designs to synthesize a candidate compound for a new gastric acid inhibitor with a better binding affinity than existing drugs. Their findings, published in Communications Biology, suggest a new way to work in tandem with AI to develop pharmaceuticals.
Stomach acid is a crucial component of food digestion. However, when the balance of gastric mucosal secretion is disturbed, stomach acid can cause discomfort and, in severe cases, conditions such as gastric ulcers and reflux esophagitis. Therefore, many people turn to gastric acid suppressants, most of which target the gastric proton pump responsible for gastric acid secretion. These drugs help neutralize stomach acid, providing relief for people suffering from heartburn and related conditions.
A collaborative research group led by Associate Professor Kazuhiro Abe and Professor Satoshi Yokoshima of the Graduate School of Pharmaceutical Sciences at Nagoya University, in collaboration with Intage Healthcare Corporation and the SPring-8 radiation facility, took a novel approach to drug development. They focused on the steric structure of the gastric proton pump, a complex protein structure in the stomach lining that transports the H+ protons that make up HCl, the acid that makes up gastric acid. They analyzed it using “Deep Quartet,” an artificial intelligence-driven drug discovery platform.
Using the AI, the researchers designed new candidate compounds with unique chemical structures to effectively target the gastric proton pump. The team aimed to identify compounds that could simultaneously bind to multiple sites on the proton pump, enhancing the overall effectiveness of the drug. They chemically synthesized these candidate compounds and analyzed their binding structures to proteins using cryo-electron microscopy. Then, the compounds were further modified to improve their binding ability.
The researchers used AI to generate more than 100 candidate compounds with unique chemical structures. Expert chemists and structural biologists then selected the most promising candidates for synthesis and tested how strongly they bound and inhibited the gastric proton pump, ultimately revealing that the sixth compound synthesized (DQ-06) exhibited stronger binding than existing reference compounds.
Despite initial reservations, the technology won Abe over. “I was skeptical when I saw some of the strange chemical structures, including DQ-02 (the second one they tested) and related ones,” he said. “But we suspected there must be a reason AI suggests such strange chemicals. We noticed that the first had a narrow binding site compared to the second, so we realized that AI was quite ‘honest’ in its approach, designing for the given binding site, which is flexible.”
Furthermore, to gain insights into the binding mechanism, the research group employed cryo-electron microscopy to visualize the molecule’s interaction with the gastric proton pump. They discovered that there was room for further improvement in the binding strength. Based on this knowledge, a new compound, DQ-18, was synthesized by introducing a chlorine atom into DQ-06, resulting in even stronger binding.
“While the results confirmed that the compound was bound as expected, we found that there was still some room between the binding pocket of the compound and the protein,” Abe said. “If we fill these gaps, the compound will fit more ‘snugly’ into the pocket, resulting in stronger bonding.”
This innovative approach led to the creation of a compound with a binding affinity nearly 10 times higher than that of SCH28080, a prototype compound for gastric acid inhibitors. Abe believes that this shows the importance of the synergy between humans and AI in drug discovery. “We can see AI being useful for creating treatments, but not completely or automatically,” he said. “We used AI for structure-based drug design, which we humans are not so good at. But we chose real candidates to synthesize, and indeed we improved it with our own hands. We efficiently used AI for what we are not good at. But I believe, at least for the time being, human knowledge is ultimately required to make any final decision.”
Their research represents a significant step forward in the development of pharmaceuticals, promising more efficient and reliable treatments for gastric acid-related conditions and inspiring fresh approaches to drug discovery. The collaboration between researchers and artificial intelligence showcases the potential of AI to revolutionize the world of medicine and improve human health as a collaborative tool alongside scientists.