Publisher Health

Researchers at Karolinska Institutet in Sweden have developed a method to study liver function and disease without requiring invasive procedures. After transplanting liver cells into the eye of mice, the cornea can be used as a window into the body to monitor liver health over time. The study is published in the journal Nature Communications.
Imagine if it were possible to study liver cells in a living organism without the need for invasive procedures. Researchers have now shown that this is possible in mice by transplanting small 3D cell cultures of liver cells, known as spheroids, into the anterior chamber of the eye. The cornea of the eye is then used as a window into the body to get clues about changes in the liver during the mouse’s lifetime.
A marker for fatty liver disease
The researchers were able to show that the liver cells attach to the iris of the eye and are supplied with blood vessels and nerves necessary for their function and survival. They also retain their typical liver characteristics and appear to reflect the health of the animal’s liver. For example, the spheroids in the eye were found to store fat in a similar way to the liver of the same animal when fed a high-fat diet, meaning that the implant could act as a marker for fatty liver disease.
“This is a unique approach that opens up new opportunities to study the role of the liver in metabolic diseases such as obesity, type 2 diabetes and fatty liver disease,” says Noah Moruzzi, assistant professor at the Department of Molecular Medicine and Surgery, Karolinska Institutet and corresponding author of the paper. “In order to stop or delay disease progression, we need to identify early disease mechanisms, but it has previously been difficult to study the liver without using invasive methods.”
Test different treatments
Metabolic diseases have increased dramatically in recent years and were previously associated with old age, but today they increasingly develop in younger individuals and obese children. These disorders share similar risk factors and are often presented together in patients with metabolic syndrome. Fatty liver and type 2 diabetes are characterised by dysfunctional lipid metabolism and blood sugar regulation, controlled by the liver and pancreas, respectively.

“Therefore, continuous and detailed monitoring of functional changes in these organs is essential to identify disease mechanisms,” says first author Francesca Lazzeri-Barcelo, PhD student at the same department. “With the new platform, we can now monitor the development of fatty liver at the cellular level and we are excited to start using it to test different drugs and treatment strategies.”
Powerful research tool
Professor Per-Olof Berggren’s research group at Karolinska Institutet has been transplanting cells and mini-organs to the anterior chamber of the eye in mice since 2008.
“In recent years, our method has proven to be a powerful research tool for monitoring the insulin-producing pancreatic islets during the development of type 2 diabetes,” he says. “Now the platform has been extended to liver research, which shows that there is potential to use the tool also in other medical areas.”
The study was financed by, among others, the European Research Council (ERC), the Erling Persson Foundation, the Knut and Alice Wallenberg Foundation, Karolinska Institutet, Jonas and Christina af Jochnick Foundation, the Swedish Diabetes Association, the Swedish Research Council and the Novo Nordisk Foundation.
Per-Olof Berggren is the co-founder and CEO of Biocrine AB. Coauthors Ingo Leibiger and Barbara Leibiger are consultants for the same company. Volker Lauschke is a co-founder, CEO, and shareholder of HepaPredict AB, as well as a co-founder and shareholder of PersoMedix AB. The remaining authors declare no competing interests.

A team of University of Wisconsin-Madison scientists has developed the first 3D-printed brain tissue that can grow and function like typical brain tissue.
It’s an achievement with important implications for scientists studying the brain and working on treatments for a broad range of neurological and neurodevelopmental disorders, such as Alzheimer’s and Parkinson’s disease.
“This could be a hugely powerful model to help us understand how brain cells and parts of the brain communicate in humans,” says Su-Chun Zhang, professor of neuroscience and neurology at UW-Madison’s Waisman Center. “It could change the way we look at stem cell biology, neuroscience, and the pathogenesis of many neurological and psychiatric disorders.”
Printing methods have limited the success of previous attempts to print brain tissue, according to Zhang and Yuanwei Yan, a scientist in Zhang’s lab. The group behind the new 3D-printing process described their method today in the journal Cell Stem Cell.
Instead of using the traditional 3D-printing approach, stacking layers vertically, the researchers went horizontally. They situated brain cells, neurons grown from induced pluripotent stem cells, in a softer “bio-ink” gel than previous attempts had employed.
“The tissue still has enough structure to hold together but it is soft enough to allow the neurons to grow into each other and start talking to each other,” Zhang says.
The cells are laid next to each other like pencils laid next to each other on a tabletop.

“Our tissue stays relatively thin and this makes it easy for the neurons to get enough oxygen and enough nutrients from the growth media,” Yan says.
The results speak for themselves — which is to say, the cells can speak to each other. The printed cells reach through the medium to form connections inside each printed layer as well as across layers, forming networks comparable to human brains. The neurons communicate, send signals, interact with each other through neurotransmitters, and even form proper networks with support cells that were added to the printed tissue.
“We printed the cerebral cortex and the striatum and what we found was quite striking,” Zhang says. “Even when we printed different cells belonging to different parts of the brain, they were still able to talk to each other in a very special and specific way.”
The printing technique offers precision — control over the types and arrangement of cells — not found in brain organoids, miniature organs used to study brains. The organoids grow with less organization and control.
“Our lab is very special in that we are able to produce pretty much any type of neurons at any time. Then we can piece them together at almost any time and in whatever way we like,” Zhang says. “Because we can print the tissue by design, we can have a defined system to look at how our human brain network operates. We can look very specifically at how the nerve cells talk to each other under certain conditions because we can print exactly what we want.”
That specificity provides flexibility. The printed brain tissue could be used to study signaling between cells in Down syndrome, interactions between healthy tissue and neighboring tissue affected by Alzheimer’s, testing new drug candidates, or even watching the brain grow.

“In the past, we have often looked at one thing at a time, which means we often miss some critical components. Our brain operates in networks. We want to print brain tissue this way because cells do not operate by themselves. They talk to each other. This is how our brain works and it has to be studied all together like this to truly understand it,” Zhang says. “Our brain tissue could be used to study almost every major aspect of what many people at the Waisman Center are working on. It can be used to look at the molecular mechanisms underlying brain development, human development, developmental disabilities, neurodegenerative disorders, and more.”
The new printing technique should also be accessible to many labs. It does not require special bio-printing equipment or culturing methods to keep the tissue healthy, and can be studied in depth with microscopes, standard imaging techniques and electrodes already common in the field.
The researchers would like to explore the potential of specialization, though, further improving their bio-ink and refining their equipment to allow for specific orientations of cells within their printed tissue..
“Right now, our printer is a benchtop commercialized one,” Yan says. “We can make some specialized improvements to help us print specific types of brain tissue on-demand.”
This study was supported in part by NIH-NINDS (NS096282, NS076352, NS086604), NICHD (HD106197, HD090256), the National Medical Research Council of Singapore (MOH-000212, MOH-000207), Ministry of Education of Singapore (MOE2018-T2-2-103), Aligning Science Across Parkinson’s (ASAP-000301), the Bleser Family Foundation, and the Busta Foundation.

Many bacteria form an antibiotic-resistant slime. Research detailing that slime’s structure could help lead to new treatments.
Bacteria are traditionally imagined as single-cell organisms, spread out sparsely over surfaces or suspended in liquids, but in many environments the true bacterial mode of growth is in sticky clusters called biofilms. Biofilm formation can be useful to humans — it is integral, for example, to the production of kombucha tea. But it is more often problematic, because it makes it more difficult to control bacterial growth: When bacterial cells produce a biofilm, it acts as a shield against outside invaders, making the bacteria more tolerant to antibiotics.
Until recently, researchers had assumed that bacteria were arranged somewhat randomly in biofilms, insofar as they had thought about the question of biofilm structure at all. But new research from Columbia University biology professor Lars Dietrich’s lab shows that bacteria that form biofilms actually have a highly structured arrangement within those slimy matrices.
Their unexpected finding could pave the way for developing new drugs that better target antibiotic-resistant bacteria.
“There’s a yin-yang trade-off for bacteria that form biofilms, since the biofilm guards against antibiotics and other threats, but also prevents food from entering and feeding the system,” said Professor Lars Dietrich, a lead author on the paper. “This research gives us an important foundation for understanding how to affect bacterial-cell arrangement and assess how to make them more susceptible to antibiotics.”
The new study, published in the journal PLOS Biology, details research conducted in professor Dietrich’s lab, spearheaded by graduate student Hannah Dayton. The paper looked specifically at an important, common pathogen, called Pseudomonas aeruginosa.
The team used scanning electron microscopy and fluorescence microscopy paired with cell labeling to conduct their research. They found that P. aeruginosa cells in biofilms are packed lengthwise and arranged perpendicularly to their growth substrate, the material that the bacteria live on and that contains the substance they are eating to survive and grow. They also found that mutations that modify the bacterial cell surface disrupt this arrangement.

When they tested the effects of a sugar added from the outside to a fully formed biofilm, they observed that its distribution was affected by the biofilm anatomy. Mutant bacteria with a disordered cellular arrangement were more responsive to added sugar or antibiotic in specific areas within the biofilm, also known as subzones. Finally, they showed that changes in biofilm anatomy shift the location of peak metabolic activity within the structure.
Together, these observations indicate that biofilm microstructure is a property that can be tuned to influence the metabolism of resident bacterial subpopulations and affect the overall survival of the group. The findings have implications for our approaches to treating infections caused by P. aeruginosa and other biofilm-forming pathogens.
The research was conducted in collaboration with the research groups of Wei Min, a Columbia chemistry professor; Raju Tomer, a Columbia biology professor; Jasmine Nirody, professor at the University of Chicago; and Anuradha Janakiraman, professor at the City University of New York (CUNY).
“The arrangement of cells is generally an underappreciated aspect of biofilm formation,” said Dayton. “We now know that it allows bacteria in biofilms to control their physiological states and has consequences for their survival during antibiotic treatment.”
“This is a promising development for the pernicious and growing problem of antibiotic resistant bacteria,” said Dietrich.

Researchers at the Centre for Genomic Regulation (CRG) in Barcelona and the Spanish National Cancer Research Centre (CNIO) in Madrid have captured the world’s first high-resolution images of the earliest moments of microtubule formation inside human cells. The findings, published today in the journal Science, lay the foundations for potential breakthroughs in treating many different types of diseases ranging from cancer to neurodevelopmental disorders.
“Microtubules are critical components of cells, but all the images we see in textbooks describing the first moments of their creation are models or cartoons based on structures in yeast. Here we capture the process in action inside human cells. Now that we know what it looks like, we can explore how it’s regulated. Given the fundamental role of microtubules in cell biology, this could eventually lead to new therapeutic approaches for a wide range of disorders,” explains ICREA Research Professor Thomas Surrey, main co-author of the study and researcher at the Centre for Genomic Regulation.
Molecular ‘highways’ of the cell
A cell is much like a bustling city, requiring state-of-the-art infrastructure to function. One of the most important components are microtubules, tubes made of proteins which act like bridges or roads that help move things around and give the cell its shape. Importantly, they are critical for cell division, ensuring that two new cells can be born from a parent cell. In neurons, they are absolutely essential, forming highways for transport over long distances.
Microtubules are built by a large assembly of proteins known as the gamma-tubulin ring complex (γ-TuRC). The proteins work like a blueprint, laying down tiny building blocks called tubulins in a specific order. This is a process called microtubule nucleation, which is like laying the foundation stones of a bridge. Once the foundation is set, tubulins are added to make the bridge as long as necessary.
For the cell to work correctly, microtubules need to be made of thirteen different rows of tubulins. A few years ago, researchers were baffled to discover that human γ-TuRC exposes fourteen rows of tubulins. This was confusing because researchers expected it to be a perfect template for microtubules, which did not seem to be the case. But high-resolution structures had only been pictured of either γ-TuRC or microtubules in isolation and never together – until now.
“We had to find conditions that allowed us to image over a million microtubules in the process of nucleation before they grow too long and obscure the action of γ-TuRC. We were able to achieve this using the molecular toolbox of our lab and then freeze the microtubule stubs in place”, explains Cláudia Brito, postdoctoral researcher at the CRG and co-first author of the study.

High-resolution imaging
To observe γ-TuRC while it was actively forming microtubules, researchers prepared samples at the CRG in Barcelona and the Electronic Microscopy Center at ALBA (EMCA), where they were flash-frozen in a thin layer of ice – preserving the natural shape of the molecules involved and helping discern fine details of structures at near atomic level. Frozen samples were then sent to the Basque Resource for Electron Microscopy (BREM) in Vizcaya, where the high-resolution data generated was then transferred to be analysed at the CNIO in Madrid. Marina Serna, Staff Scientist at CNIO and co-first author of the study, used the images obtained by cryo-electron microscopy and complex image processing methods to determine the 3D structure of γ-TuRC while forming microtubules.
This analysis revealed that as γ-TuRC starts the nucleation process and as the microtubule begins to form, it cleverly changes its shape. Initially in an open state, it progressively closes as the microtubule grows. The change makes γ-TuRC stow away one of its 14 tubulins, effectively matching the design of the microtubule that needs only 13 rows. The whole process is facilitated by a newly-discovered latch mechanism, revealing that it’s the growing microtubule itself which helps the template find its correct shape.
Oscar Llorca, Director of the Structural Biology program at CNIO and main co-author of the paper, explains: “We have visualized the process that initiates microtubule formation, and we see that human γ-TuRC is an open ring that closes to effectively become a perfect template to nucleate microtubules. But we also discovered that this ring, in order to close, needs the ‘first brick’ of a microtubule to be put in place; when this happens, a region of the human γ-TuRC acts as an anchor that engages this ‘first brick’ to then close the ring and launch the formation of the microtubules”.
Implications for human health and disease
The most well-known consequence of microtubule malfunction is cancer, a disease characterised by uncontrolled cell proliferation. Neurodevelopmental disorders such as microcephaly also occur when microtubule processes go wrong, as well as other conditions ranging from respiratory problems to heart disease.
Some cancer drugs work by targeting microtubules, preventing them from disassembling or forming in the first place. However, these disrupt microtubules indiscriminately in both cancerous and healthy cells, leading to side effects. Tumours also develop resistance to these drugs.
The findings of the study are important because understanding the precise mechanism of how microtubules are laid down could lead to the development of more targeted and effective cancer treatments, as well as new therapies for a broader range of conditions.
“The process of nucleation decides where the microtubules are in a cell and how many you have in the first place. It is likely that the conformational changes we observe are controlled by yet-to-be-found regulators in cells. Several candidates have been described in other studies, but their mechanism of action is unclear. As further work clarifies how regulators bind to γ-TuRC and how they affect the conformational changes during nucleation, it may transform our understanding of how microtubules work, and eventually offer alternative sites that one might want to target to prevent cancer cells from going through the cell cycle,” concludes Dr. Surrey.

For centuries, doctors have used their hands as essential diagnostic tools — exploring joints and palpating abdomens to assess a patient’s health. Often a cancer will reveal itself as a lump or unusual stiffness in a normally bouncy tissue or organ.
More recently, the relationship between stiffness and cancer has been documented through biophysical studies and clinical trials, particularly in liver and breast cancer. For example, stiffness is a primary hallmark of liver cirrhosis, which can progress to liver cancer.
Now researchers at Stanford University have shown that another biophysical characteristic known as viscoelasticity — think of how stretching a ball of Silly Putty or a clump of bread dough is met at first with resistance, and then with release — is even more tightly correlated with liver cancer than stiffness, particularly in people with Type 2 diabetes.
The distinction matters because people with Type 2 diabetes are two to three times as likely as people without diabetes to develop liver cancer, which often occurs in the absence of cirrhosis. Liver cancer rates are increasing in part because the prevalence of diabetes is growing worldwide, particularly in marginalized communities where healthy food choices and opportunities for regular exercise are scarce.
“This is the first time that the dogma of matrix stiffness as a primary predictor of liver cancer is being challenged,” said professor of gastroenterology and hepatology Natalie Torok, MD. “Current guidelines recommend routine liver cancer screening only for people with cirrhosis. As a result, many people with Type 2 diabetes are not screened at all. These new findings have major implications not just for liver cancer, but also other cancers for which diabetes is a risk factor, including breast cancers.”
Torok is the senior author of the study, which was published online Jan. 31 in Nature. Postdoctoral scholar Weiguo Fan, PhD, is the lead author.
Torok and her colleagues collaborated with researchers in the laboratory of associate professor of mechanical engineering Ovijit Chaudhuri, PhD, to investigate the role of viscoelasticity in liver cancer in patient samples, animal models and cells grown in the laboratory in a Jell-O-like tissue scaffolding called a hydrogel.

“This study is the first on the role of viscoelasticity in cancer with data that spans from humans and mouse models to in vitro 3D culture studies and computational simulations,” Chaudhuri said. “It definitively establishes the role of viscoelasticity in liver cancer progression.”
The study was supported by Stanford Medicine’s SPARK Program in Translational Research and its Innovative Medicines Accelerator, complementary programs meant to streamline the path of promising academic laboratory discoveries to clinical applications that benefit patients.
Stiffness test
Liver stiffness is measured non-invasively with imaging techniques called transient elastography or MR elastography involving a vibrating pad placed on the abdomen. The vibrations are transmitted from the imaging probe to the organ; the wave of vibration moving through a stiff medium differs from one moving through something more malleable. People with a liver stiffness that exceeds a certain threshold are diagnosed with liver cirrhosis; current guidelines recommend that they be screened every six months for liver cancer with an abdominal ultrasound and blood tests.
Measurements such as stiffness arise from what’s called the extracellular matrix — the space between and around an organ’s cells that is chock-a-block with proteins, sugars and minerals.
“Our organs are not just clumps of cells,” Chaudhuri said. “The cells exist in a scaffolding called the extracellular matrix that gives them physical support but also affects their maturation, specialization and functioning.”
Like a grade-school teacher, the matrix provides a physical framework that supports and organizes the cells, gentling and channeling them to harmoniously create a functional tissue. When the matrix is disrupted, any bad-apple cancerous or pre-cancerous cells more readily lose their way, spreading to places they shouldn’t; dividing uncontrollably; or morphing in to other, more dangerous versions of themselves.

People with diabetes have elevated levels of what are called advanced glycation end products, or AGEs. AGEs arise when blood sugar is poorly controlled and elevated levels of sugar molecules known as glucose begin to glom onto nearby proteins including collagen — a key structural component of the extracellular matrix. (AGEs are also present in protein- or fat-rich foods or in foods prepared at high heat such as frying or broiling.)
The researchers found that liver samples from people with Type 2 diabetes had higher levels of AGEs and were more viscoelastic — but no more stiff — than liver samples from people without Type 2 diabetes. A closer look in laboratory mice showed animals fed a diet high in AGEs had shorter and less interconnected collagen fibers in the liver’s extracellular matrix than those found in animals fed standard chow.
Next, the researchers studied how cells behaved when grown in the laboratory in a three-dimensional gel to mimic liver matrix structure. Tinkering with the cells outside the body allowed them to assess the effect of various changes in their growth and behavior.
“In our engineered hydrogels, we can tune one biophysical property such as viscoelasticity or stiffness at a time to understand how each property impacts the cells,” Chaudhuri said. “We saw that a change in viscoelasticity alone is enough to drive a more invasive behavior in the cells.”
In particular, the researchers noted that a more viscoelastic matrix promotes changes in liver cell shape and allows the formation of invasive protrusions on their membranes that help them escape natural barriers meant to keep cells in their rightful places.
Paradigm shift
Finally, Torok and her colleagues went one step further, dissecting a series of cellular signals that promote liver cancer progression in viscoelastic conditions that includes a cancer-associated protein called YAP.
“This is the first time that changes in collagen structure have been proven to promote viscoelasticity and liver cancer progression independent of stiffness,” Torok said. “It’s a complete change in paradigm that could explain the greater risk of liver cancer in people with Type 2 diabetes and may help select people should undergo regular liver cancer screening.”
Fortunately, like stiffness, viscoelasticity can be assessed non-invasively with MR elastography by changing a few parameters in vibration frequency and measurement. Torok is planning to launch a clinical trial to further study viscoelasticity, Type 2 diabetes and liver cancer progression.
“One of the major questions in medicine today is why people with diabetes and fatty liver disease are so prone to liver cancer, and how we can address this,” Torok said. “Our research suggests that many more people, particularly those with diabetes, should be screened for cancer. If we did that, perhaps we could act earlier and save lives.”
Researchers from Purdue University; Tsinghua University in Beijing; the University of Pittsburgh; the University of California, Davis; Albert Einstein College of Medicine; Keio University in Yokohama; and the University of Pennsylvania contributed to the work.
The study was funded by the National Institutes of Health (grants R01DK083283, RO1CA277710, 1RO1AG060726, R37 CA214136, 1R01CA251155, 1R01CA204586 and 1R01GM126256) and a Stanford SPARK award.

The study, led by a team based at the University of York and Hull York Medical School and at Tees, Esk and Wear Valleys NHS Foundation Trust, found levels of depression reduced significantly and the benefits were greater than those seen for antidepressants.
Participants in the study reported their levels of emotional loneliness fell by 21% over a three-month period and the benefits remained after the phone calls had ceased, suggesting an enduring impact.
The Behavioural Activation in Social Isolation trial (BASIL+ trial) started within months of the 2020 pandemic and was the largest trial ever undertaken to target and measure loneliness in this way. The study, published in the journal The Lancet (Healthy Longevity), represents a rapid advance in evidence to understand what works in preventing loneliness.
People invited to take part in the BASIL+ study were aged over 65 with multiple long-term conditions. They had been asked to shield during COVID and were at a high risk of loneliness and depression.
The trial was supported by a £2.6M award from the National Institute for Health and Care Research (NIHR) and was the only mental health trial prioritised by the NHS as part of its Urgent Public Health programme — a cornerstone of its fight against COVID. Hundreds of older people were recruited to the trial from 26 sites across the UK during the COVID pandemic of 2020-21.
Politicians and policy makers have become increasingly aware of the importance of loneliness, but have struggled to know “what works” in its prevention. The World Health Organization has just declared loneliness to be a ‘Global Health concern’ and has launched an international commission on the problem. It is anticipated that the results of the BASIL+ trial will feed into this process, since BASIL+ is the largest trial ever undertaken to combat loneliness. The Jo Cox Commission, established in memory of the murdered politician, estimates that 9 million people are affected by loneliness in the UK and there is a cross governmental strategy to tackle loneliness, with a Ministerial appointment.
The research was jointly led by Professor Simon Gilbody from the University of York and Hull York Medical School and Professor David Ekers from Tees, Esk and Wear Valleys NHS Foundation Trust. Professor Gilbody said: “We now know that loneliness is as bad for your health as smoking 15 cigarettes a day and depression is a silent killer. All of us working on the BASIL+ trial had older parents and relatives who became socially isolated during lockdown.”
“Based on our previous research, we had a good idea what might work,” Professor Ekers added. “With the support of the NHS and the NIHR we were able to test this in a large rigorous trial. The results are now available and this is very exciting. The UK led the world with the vaccine discovery trials. Similarly in mental health we have advanced the science of ‘what works’ in the area of loneliness, and we have learned much from the dark days of the pandemic.'”

Professor Ekers, Honorary Professor at the Mental Health and Addictions Research Group at the University of York and Professor Dean McMillan, Professor of Clinical Psychology at Hull York Medical School and University of York designed and led the telephone support programme. Professor McMillan said “an ounce of prevention is worth a pound of cure, and this trial shows how we can prevent both depression and loneliness.”
Professor Lucy Chappell, CEO of the National Institute for Health and Care Research, which funded the study, said: “These results are an important step forward in understanding what works in tackling and preventing loneliness and depression. The research is also a great example of how public money allows researchers, healthcare professionals and the public to work together across institutions and organisations to deliver results that will really make a difference to people’s health and wellbeing.”
Dr Liz Littlewood, the BASIL+ trial manager from the Department of Health Sciences, University of York, added: “This is what the UK does well and it shows how the NHS, Universities and third sector organisations were able to work in partnership during the pandemic to tackle the big health challenges.”
The BASIL+ partnership included leading researchers from the Universities of Leeds, Keele, and Manchester and also the charity AgeUK.

Published1 hour agoShareclose panelShare pageCopy linkAbout sharingImage source, Getty ImagesBy Duncan KennedyBBC NewsThe rate of improvement in the number of people who survive cancer has slowed significantly, a study says.A report by Cancer Research UK says the rate of progress was five times faster in the 2000s than in the 2010s.It says lack of sufficient funding for research is largely to blame.However, the report also finds the likelihood of surviving a decade or more with cancer in the UK is the highest it has ever been, rising from 47.9% in 2010-11 to 49.8% in 2018.This compares to about a quarter (24%) in the early 1970s.It is the first time in a decade that the charity has published figures on overall cancer survival rates in the UK.’High’ survival for stage 1-3 cancersCancer survival in the UK ‘lagging behind’Thousands dying needlessly of cancer, says charityScreening programmes for breast, bowel and cervical cancer are credited with saving more than 5,000 lives a year.Research has also led to improvements in prevention, diagnosis, and treatment. But the report estimates that unless government spending levels for research are maintained over the next 10 years, there will be a funding gap of more than £1bn, which could “put further medical advances at risk”.Jon Shelton, head of cancer intelligence at Cancer Research UK, said: “This report shows us where the UK is doing well, and where we need to focus on improvements for patients. There are positives in here – screening is having a real impact, and cancer mortality rates are falling. “There are many areas to improve though. Cancer survival is not improving quickly enough. People are waiting far too long for diagnosis and to start treatment, with cancer waiting time targets consistently being missed. And we need to prevent more cancers.” The report says smoking remains the biggest cause of cancer in the UK, with 150 cases in the UK every day. Meanwhile obesity and being overweight causes about 22,800 cases of cancer every year in the UK and is a risk factor for 13 different types of the illness, the report says. Cancer Research UK says a “national cancer council” should be set up for England, bringing together the government, scientists, and charities, to create a 10-year cancer strategy.It says that by 2040 there are projected to be 500,000 new cancer cases diagnosed each year in the UK – mainly because of a growing and ageing population.But about a quarter of cancers in England over the last decade have been diagnosed as an emergency – and cancers first spotted via this route are more likely to have late-stage disease, which affects their treatment options. The analysis for this new report was carried out for Cancer Research UK by the Cancer Survival Group, based at the London School for Hygiene and Tropical Medicine.Cancer Research UK says for every £1 invested in research, £2.80 of economic benefits are generated.A Department of Health spokesperson said: “We welcome the news that record numbers of people are surviving cancer long term, with people being diagnosed earlier and the NHS treating record numbers of cancer patients over the past two years. “But we know there is more work to do.”We are working to make access to cancer services faster and simpler. We have also invested £2.3bn into speeding up diagnosis and launched 153 community diagnostic centres across England.”More on this story’High’ survival for stage 1-3 cancersPublished24 January 2019Cancer survival in the UK ‘lagging behind’Published12 September 2019Thousands dying needlessly of cancer, says charityPublished28 November 2023Related Internet LinksCancer Research UKThe BBC is not responsible for the content of external sites.

Published1 hour agoShareclose panelShare pageCopy linkAbout sharingImage source, PA MediaBy Helen Burchell and PA MediaBBC News, CambridgeshireA woman who received a lung transplant as she was “suffocating with every breath” credited a system to prioritise urgent cases with saving her life.The UK Lung Allocation Scheme (Uklas) was introduced in 2017, categorising patients by need.Georgie Cooper, 26, of Chelmsford, said being moved to the “urgent” list for a transplant made her feel “reborn”.A study of the system at Royal Papworth Hospital in Cambridge found the odds of a transplant greatly increased.The Uklas scheme was introduced by NHS Blood and Transplant (NHSBT).It categorises patients’ needs into three groups – “super urgent”, “urgent” and “non-urgent” – and also cuts out geographical boundaries. The study looked at results after the scheme was introduced in 2017, and before.Researchers found the odds of receiving a transplant within six months increased by 41% after the initiative.Image source, PA MediaThey examined data on lung transplants across the UK between March 2015 and November 2016 – before the scheme was introduced – and from May 2017 to January 2019.They found 461 patients joined the lung transplant waiting list in the first period, and 471 after Uklas was launched.Before 2017, the average waiting time for donor lungs was 427 days.After the scheme’s launch, “super urgent” patients waited an average of eight days for transplant and “urgent” patients 15 days.Ms Cooper was categorised as “urgent” need and received a lung transplant in 2021.She has cystic fibrosis and, by the time of her transplant, was considered just weeks from death.”Before my transplant I was suffocating with every breath I tried to take,” said Ms Cooper.”I am so happy I could be prioritised for an urgent transplant.”Knowing that if you get sicker, the system adjusts, really helps. “I feel reborn. I am so grateful to the donor and their family – they are my heroes.”Image source, PA MediaHowever, those in the “non urgent” category had longer average waits with many waiting for more than a year-and-a-half (585 days).The study found the proportion of people who died while on the waiting list reduced from 15% to 13% after the scheme was launched.Post-transplant survival also increased: before the scheme was launched about 81% of patients survived for at least a year, rising to 83% after Uklas was rolled out.Image source, PA MediaOne of the study’s authors, Jasvir Parmar, a transplant consultant at Royal Papworth Hospital, said: “The new policy has fulfilled its goals of prioritising the most critically ill and improving the odds of transplantation.”Dale Gardiner, of NHS Blood and Transplant, said: “The revised lung allocation scheme was developed to ensure timely allocation of donor lungs to those most in need.”He encouraged more people to register as donors.Follow East of England news on Facebook, Instagram and X. Got a story? Email eastofenglandnews@bbc.co.uk or WhatsApp 0800 169 1830More on this storyPioneer doctor has no ‘magical’ healthcare answerPublished19 hours agoTeen heart-lung transplant a UK first, says hospitalPublished1 June 2023Robot to carry out hospital’s thoracic surgeryPublished23 March 2023Related Internet LinksNHS Organ DonationRoyal Papworth HospitalThe BBC is not responsible for the content of external sites.

New findings in The American Journal of Pathology, published by Elsevier, report that a class of small RNAs (microRNAs), microRNA-29, can restore normal skin structure rather than producing a wound closure by a connective tissue (scar). Any improvement of normal skin repair would benefit many patients affected by large-area or deep wounds prone to dysfunctional scarring.
Because the burden of non-healing wounds is so significant, it is sometimes called a “silent pandemic.” Worldwide, costs associated with wound care are expected to reach US$15 to 22 billion per year by 2024, exceeding the cost of managing obesity-related health problems in some parts of the world.
Lead investigator Svitlana Kurinna, PhD, Division of Cell Matrix Biology and Regenerative Medicine, FBMH, University of Manchester, explained, “We had data showing that microRNAs can regulate skin growth. microRNAs do not code for proteins, so it wasn’t clear exactly how such small molecules can make changes to the skin. We therefore studied underlying mechanisms that could be targeted to improve cutaneous wound healing.”
The molecular events during early wound healing stages of inflammation and tissue formation have been well described using single cell sequencing and proteomic approaches. microRNAs are important factors in healing and may regulate functions in skin repair; however, the mechanisms underlying tissue remodeling are unclear. Scientists studying wound healing in microRNA-29 gene knockout transgenic mice suggest that the release of microRNA-29 targets promotes wound healing by regulating skin regeneration by binding long RNAs coding for structural protein laminin C2 (LAMC2) of the skin. This restores the normal skin structure rather than creating a connective tissue scar.
In the current study, researchers noted that wild type wounded mice healed quite well, but the skin of transgenic mice devoid of microRNA-29 regenerated even better. To understand the reasons, they conducted in-depth microscopic analysis of the transgenic wounds. They observed deposition of LAMC2 — usually found in one of the skin layers in wild mice — around blood vessels inside the wounds of microRNA-29-deficient transgenic mice. This observation indicates that microRNA-29 may be inhibiting the expression of LAMC2, and deletion in the transgenic mice relieved the inhibition, which resulted in faster wound healing.
Dr. Kurinna noted, “These processes are likely mediated by microRNA-29 target microRNAs released upon removal of microRNA-29 to improve cell matrix adhesion. These results further suggest a link between LAMC2, improved angiogenesis, and re-epithelialization. We had expected a different change in skin regeneration; we thought the removal of microRNA-29 would help outer layers of the skin to grow faster, but it was the deep matrix of the wound that showed an improvement.
These findings in both mice and humans demonstrate the role of microRNA-29 in epidermal repair and suggest that the release of microRNA-29 targets, particularly LAMC2, promotes wound healing. The inhibition of microRNA-29 and/or overexpression of LAMC2 may be a new and effective strategy for improving wound healing.
Dr Kurinna concluded, “Our findings are of particular interest because they show the mechanism to restore normal skin structure rather than a wound closure by a connective tissue (scar). Any improvement of normal skin repair would therefore help many patients affected by large-area or deep wounds prone to dysfunctional scarring.”

Somewhere between 24 and 50 million Americans have an autoimmune disease, a condition in which the immune system attacks our own tissues. As many as 4 out of 5 of those people are women.
Rheumatoid arthritis, multiple sclerosis and scleroderma are examples of autoimmune disorders marked by lopsided female-to-male ratios. The ratio for lupus is 9 to 1; for Sjogren’s syndrome, it’s 19 to 1.
Stanford Medicine scientists and their colleagues have traced this disparity to the most fundamental feature differentiating biological female mammals from males, possibly paving the way for a better way to predict autoimmune disorders before they develop.
“As a practicing physician, I see a lot of lupus and scleroderma patients, because those autoimmune disorders manifest in skin,” said Howard Chang, MD, PhD, professor of dermatology and of genetics and a Howard Hughes Medical Institute investigator. “The great majority of these patients are women.”
Chang, the Virginia and D.K. Ludwig Professor in Cancer Research and director of the RNA Medicine Program, is the senior author of the study, to be published Feb. 1 in Cell. Basic life research scientist Diana Dou, PhD, is its lead author.
The silence of the second X
Women have too much of a good thing: It’s called the X chromosome.

Throughout the mammalian kingdom, biological sex is determined by the presence, in every female cell, of two X chromosomes. Males cells pack just one X chromosome, paired with a much shorter one designated the Y chromosome.
The stubby Y chromosome contains only a handful of active genes. It’s quite possible to live a full life without a Y chromosome. In fact, more than half of the people on Earth — women — lack Y chromosomes and do just fine. But no mammalian cell, male or female, can survive without at least one copy of the X chromosome, which holds many hundreds of active protein-specifying genes.
Still, having two X chromosomes risks the production, in every female cell, of twice the amount of the myriad proteins specified by the X but not the Y chromosome. Such massive overproduction of so many proteins would be lethal.
Nature has devised a clever, if complicated, workaround called X-chromosome inactivation. Early in embryogenesis, each cell in the nascent female mammal makes an independent decision to shut down the activity of one or the other of its two X chromosomes. Once that decision is made, it’s handed down to these cells’ progeny in the developing fetus. That way, the same amount of each X-chromosome-specified protein is produced in a female cell as in a male cell.
As the researchers discovered, X-chromosome inactivation can lead to autoimmune disorders, but other factors can also cause these disorders — which is why men sometimes develop them.
The great equalizer
X-chromosome inactivation is achieved courtesy of a molecule called Xist. The gene for Xist is present on all X chromosomes, including the single one male cells have. But Xist itself is produced only when the X chromosome that its gene resides on is one of a matched XX pair — and is produced and deployed on only one member of that pair.

Xist consists of RNA, a substance best known for being a simple-minded messenger that shuttles genes’ instructions for making proteins to the intracellular machines that make them. Yet RNA can do a whole lot more than schlep genetic information. There are as many different kinds of so-called long noncoding RNA (lncRNA) molecules — lengthy RNA stretches that don’t carry instructions for making proteins — as there are of the protein-encoding RNA variety. These lncRNA molecules can park themselves on stretches of chromosomes and change the likelihood that the cellular machinery charged with reading the genes in those locations will do so.
Xist, a type of lncRNA, is much longer than most. Xist coats long sections of one of a female mammalian cell’s two X chromosomes — but always just one — cutting that chromosome’s output to zero or close to it. The other X chromosome, left undisturbed, pumps out just enough RNA-encoded instructions to keep the cell humming.
But Xist’s nestling into the extra X chromosome generates odd combinations of lncRNA, proteins that bind to it, other proteins that bind to those proteins, and DNA some of those proteins cling to. These complexes can trigger a strong immune response, Chang and his colleagues have learned.
In 2015, Chang’s group identified close to 100 proteins that either bound to Xist or that bound to those proteins, collectively enabling this molecule to lay anchor along gene-specifying regions of the X chromosome.
Inspecting this Xist “parts list,” Chang realized that many of Xist’s collaborator proteins were known to be associated with autoimmune disorders. Might the RNA-protein-DNA complexes generated in the course of X-chromosome inactivation be triggering the notoriously high rate of autoimmunity in women compared with men? That question was the impetus for the new study.
What if males made Xist?
To eliminate possible competing causes such as female hormonal action or aberrant protein production by the supposedly silenced second X chromosome, the researchers tossed the Xist ball into the male court. They sewed the gene for Xist into the genomes of two different strains of male lab mice. One strain is quite susceptible to autoimmune symptoms mimicking lupus, with females more susceptible than males. The other is resistant to it.
The inserted Xist gene had been modified in two ways. It could be turned on or off by chemical means, pumping out Xist only when the scientists wanted it to. The Xist gene was also tweaked slightly so that its RNA product would no longer silence the genes of the male mouse’s chromosome into which it was stitched.
Merely inserting that modified Xist gene had no noticeable effect on the mice. But the Xist produced from the inserted gene, once that gene was activated, still formed characteristic complexes with almost all the proteins found earlier to be collaborating closely with Xist.
Now, the scientists could ask: Is a bioengineered male mouse that’s been coaxed to produce Xist more prone to autoimmunity than a normal male mouse, which never produces it, or than a male in whom the gene for Xist has been inserted but not activated?
By injecting an irritant known to induce a lupus-like autoimmune condition in the susceptible mouse strain, the investigators could compare its effect on males who made Xist with its effect on normal males, who made none.
In these susceptible mice, males in which the Xist gene was activated developed lupus-like autoimmunity at a rate approaching that of females — and considerably more so than non-bioengineered males.
The absence of autoimmunity in some female or Xist-activated male mice in the susceptible strain showed that not just activation of Xist but also some kind of tissue-damaging stress (caused, in this case, by injection of the irritant) is required to get the autoimmunity ball rolling.
In the autoimmune-resistant strain, activating Xist in bioengineered male mice wasn’t enough to induce autoimmunity — as might be predicted by the fact that in this strain even females seldom develop autoimmunity. That suggests that not only Xist activation but also an appropriate genetic background is necessary for autoimmunity to develop.
These constraints on autoimmunity are fortunate, because if there were none all women might be more susceptible to develop immunity, Chang noted.
Toward a better autoimmunity-screening panel
An early step in the development of autoimmunity is the appearance of autoantibodies: antibodies targeting one’s own tissues or cell products. Autoantibodies to the contents of cell nuclei are called anti-nuclear antibodies. Close examination of blood samples from about 100 patients with autoimmunity showed the presence of autoantibodies to many of the complexes associated with Xist. Some of these autoantibodies were specific to one or another autoimmune disorder, indicating their potential utility in identifying particular emergent autoimmune disorders before symptoms develop. Autoantibodies to still other Xist-associated proteins spanned several disorders, designating them as possible common markers of autoimmunity.
“Every cell in a woman’s body produces Xist,” Chang said. “But for several decades, we’ve used a male cell line as the standard of reference. That male cell line produced no Xist and no Xist/protein/DNA complexes, nor have other cells used since for the test. So, all of a female patient’s anti-Xist-complex antibodies — a huge source of women’s autoimmune susceptibility — go unseen.”
Researchers from the Johns Hopkins University School of Medicine; the KTH Royal Institute of Technology, in Stockholm; and the Swiss Federal Institute of Technology, in Zurich, contributed to the work.
The study was funded by the National Institutes of Health (grants T32AR007422, K99/R00 and T32AR050942), the Scleroderma Research Foundation and the Howard Hughes Medical Institute.