Publisher Health

It’s been hailed as a wonder drug and it’s certainly creating wonder profits. By some estimates, the Cannabidiol (or CBD) market could be worth $20 billion dollars by 2024.
While users tout its effectiveness in pain relief, up until now there’s been limited experimental human research on the actual effectiveness of the drug. However, a new study led by University researchers sheds light on the ability of CBD to reduce pain along with the impact that the so-called placebo effect may have on pain outcomes.
“For science and the public at large the question remained, is the pain relief that CBD users claim to experience due to pharmacological effects or placebo effects,” says Martin De Vita, a researcher in the psychology department in the College of Arts and Sciences. “That’s a fair question because we know that simply telling someone that a substance has the ability to relieve their pain can actually cause robust changes in their pain sensitivity. These are called expectancy effects.”
De Vita, along with Stephen Maisto, research professor and professor emeritus of psychology, were uniquely prepared to answer that exact question. The pair, along with fellow lab member and doctoral candidate Dezarie Moskal, previously conducted the first systematic review and meta-analysis of experimental research examining the effects cannabinoid drugs on pain.
As the first experimental pain trial to examine CBD, their study yielded consistent and noteworthy results. Among other findings, the data showed that CBD and expectancies for receiving CBD do not appear to reduce experimental pain intensity, but do make the pain feel less unpleasant.
De Vita and Maisto used sophisticated equipment that safely induces experimental heat pain, allowing them to measure how the recipient’s nervous system reacts and responds to it. “Then we administer a drug, like pure CBD, or a placebo and then re-assess their pain responses and see how they change based on which substance was administered,” says De Vita.

Cardiovascular disease, the most common cause of death, is the result of oxygen deprivation as blood perfusion to affected tissue is prevented. To halt the development of the disease and to promote healing, re-establishment of blood flow is crucial. Researchers at Uppsala University have now discovered that one of the most common immune cells in the human body, macrophages, play an important role in re-establishing and controlling blood flow, something that can be used to develop new drugs.
The classic function of immune cells is to defend the body against attacks from microorganisms and tumour cells. Macrophages are immune cells specialised in killing and consuming microorganisms but they have also been shown to be involved in wound healing and building blood vessels.
A new study published by researchers at Uppsala University demonstrates that macrophages accumulate around blood vessels in damaged tissue in mice, but also in humans after a myocardial infarction or peripheral ischemia. In mice, these macrophages could be seen to regulate blood flow, performing a necessary damage-control function. In healthy tissue, this task is carried out by blood vessel cells.
This discovery led the research group to investigate whether their findings could be developed into a new treatment to increase blood flow to damaged leg muscles, thus stimulating healing and improving function. By increasing the local concentration of certain signal substances that bind to macrophages in the damaged muscle, the research group was able to demonstrate that more macrophages accumulated around the blood vessels, improving their ability to regulate blood flow. This in turn resulted in improved healing and that the mice were able use the injured leg to a far greater extent.
“This is an entirely new function for the cells in our immune system and might mean that in future we can use immunotherapies to treat not only cancer but also cardiovascular diseases,” says Mia Phillipson, leader of the research group behind the discovery.
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Materials provided by Uppsala University. Original written by Linda Koffmar. Note: Content may be edited for style and length.

People with type 2 diabetes tend to have poorer muscle function than others. Now a research team at Lund University in Sweden has discovered that in type 2 diabetes, a specific gene is of great importance for the ability of muscle stem cells to create new mature muscle cells. The findings are published in Nature Communications.
“In people with type 2 diabetes, the VPS39 gene is significantly less active in the muscle cells than it is in other people, and the stem cells with less activity of the gene do not form new muscle cells to the same degree. The gene is important when muscle cells absorb sugar from blood and build new muscle. Our study is the first ever to link this gene to type 2 diabetes,” says Charlotte Ling, professor of epigenetics at Lund University who led the study.
In type 2 diabetes, the ability to produce insulin is impaired, and patients have chronically elevated blood sugar. Muscles are generally worse at absorbing sugar from food, and muscle function and strength are impaired in patients with type 2 diabetes.
A muscle consists of a mixture of fiber types with different properties. Throughout life, muscle tissue has the ability to form new muscle fibers. There are also immature muscle stem cells that are activated in connection with, for example, injury or exercise. In the current study, the researchers wanted to investigate whether epigenetic patterns in muscle stem cells can provide answers to why impaired muscle function occurs in type 2 diabetes.
Two groups were included in the study: 14 participants with type 2 diabetes and 14 healthy people in a control group. The participants in the groups were matched by age, gender and BMI (body mass index). The researchers studied epigenetic changes in the muscle stem cells in both groups, and under exactly the same conditions, they also extracted mature muscle cells and compared them. In total, they identified 20 genes , including VPS39, whose gene expression differed between the groups in both immature muscle stem cells and mature muscle cells. The researchers also compared the epigenetic patterns of muscle cells before and after cell differentiation in both groups.
“Despite the fact that both groups’ muscle stem cells were grown under identical conditions, we saw more than twice as many epigenetic changes in the type 2 diabetes group during the differentiation from muscle stem cell to mature muscle cells. Muscle-specific genes were not regulated normally, and epigenetics did not function in the same way in cells from people with type 2 diabetes,” says Charlotte Ling.
“The study clearly showed that muscle stem cells that lack the function of the gene VPS39, which is lower in type 2 diabetes, also lack the ability to form new mature muscle cells. This is because muscle stem cells that lack VPS39 due to altered epigenetic mechanisms cannot change their metabolism in the same way as muscle stem cells from controls — the cells therefore remain immature or break down and die,” says Johanna Säll Sernevi, postdoc researcher at Lund University.
To confirm the findings, the researchers also used animal models with mice that had a reduced amount of the VPS39 gene, to mimic the disease. The mice subsequently had altered gene expression and reduced uptake of sugar from blood into the muscle tissue, just like the individuals with type 2 diabetes.
The comprehensive study is a collaboration between Swedish, Danish and German researchers, who believe that the findings open up new avenues for treating type 2 diabetes.
“The genome, our DNA, cannot be changed, although epigenetics in effect does. With this new knowledge, it is possible to change the dysfunctional epigenetics that occur in type 2 diabetes. For example, by regulating proteins, stimulating or increasing the amount of the VPS39 gene, it would be possible to affect the muscles’ ability to regenerate and absorb sugar,” concludes Charlotte Ling.
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Materials provided by Lund University. Note: Content may be edited for style and length.

Researchers at the University of Cincinnati say a regulatory protein found in skeletal muscle fiber may play an important role in the body’s fight or flight response when encountering stressful situations.
The protein, fast skeletal myosin binding protein-C (fMyBP-C), plays a foundational role in the proper regulation of contractile structure and function in the body’s fast twitch muscles — these muscles produce sudden bursts of power to sprint into action, jump or lift heavy objects. Fast skeletal myosin binding protein-C modulates the speed and force of fast skeletal muscle contraction.
“This response is very critical for the higher animal and human survival. Just imagine, you are walking through a forest and suddenly you see a tiger in front of you,” says Sakthivel Sadayappan, PhD, a professor in the UC Division of Cardiovascular Health and Disease. “You will immediately act, either to fight or run away from the animal. For that action, fast muscle is essential, and fast myosin binding protein-C is the key molecule to regulate the speed of action.”
Myosin-binding protein-C is a thick filament regulatory protein found in striated muscle in both the heart and skeletal system. The protein performs different functions in the two organs, regulating contractility in the heart and playing a role in the development of fast and slow muscle fibers in skeletal muscle tissue.
Sadayappan along with researchers at UC College of Medicine, Florida State University, the University of Massachusetts Medical School and the Illinois Institute of Technology published research in the scholarly journal PNAS to further the understanding of the protein in skeletal function and regulation.
The study’s lead author is Taejeong Song, PhD, a postdoctoral fellow in the Sadayappan Lab at the UC College of Medicine.
Song says that research examined the role of the protein in fast-twitch muscles by generating a knockout mouse — an animal in which researchers have either inactivated, replaced or disrupted the existing fast myosin binding protein-C gene to study its impact.
“We found that knockout mice demonstrated a reduced ability to exercise, showed less maximal muscle force and a diminished ability for muscle to recover from injury,” explains Sadayappan. “Our study concludes that fast myosin binding protein-C is essential in regulating the force generation and speed of contraction of fast muscles.”
Song says advancing the knowledge of fast myosin binding protein-C may someday assist in addressing skeletal muscular disorders.
“Individuals lose their ability of muscle force generation for various reasons,” says Song. “They may be extremely inactive or hospitalized for long periods of time. Aging may also be the cause for some. We also think if we can manipulate the workings of fast myosin binding protein-C in skeletal muscle that we can prevent or at least slow down the loss of muscle function in genetic muscle disease such as distal arthrogryposis. Our research is trying to figure out this problem in human health.”
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Materials provided by University of Cincinnati. Original written by Cedric Ricks. Note: Content may be edited for style and length.

Researchers from Trinity College Dublin have discovered that some skeletal defects associated with a lack of movement in the womb during early development may still be ameliorated after such periods of immobility if movement resumes.
The researchers’ discovery was made using chicken embryos, which develop similarly to their human equivalents and which can be easily viewed as development takes place — raising hopes that the finding may also apply to humans and thus have important implications for therapeutic interventions.
The research has just been published in leading international journal, Disease Models and Mechanisms.
Why babies need to move in the womb
Fetal movement in the uterus is a normal part of a healthy pregnancy and previous research by the group has shown that key molecular interactions that guide the cells and tissues of the embryo to build a functionally robust yet malleable skeleton are stimulated by movement.
If an embryo doesn’t move, a vital signal may be lost or an inappropriate one delivered in error, which can lead to the development of brittle bones or abnormal joints. As such, reduced or absent movement can lead to problems with development of bones and joints including joint dysplasia and temporary brittle bone disease in infants.

Being unable to walk quickly can be frustrating and problematic, but it is a common issue, especially as people age. Noting the pervasiveness of slower-than-desired walking, engineers at Stanford University have tested how well a prototype exoskeleton system they have developed — which attaches around the shin and into a running shoe — increased the self-selected walking speed of people in an experimental setting.
The exoskeleton is externally powered by motors and controlled by an algorithm. When the researchers optimized it for speed, participants walked, on average, 42 percent faster than when they were wearing normal shoes and no exoskeleton. The results of this study were published April 20 in IEEE Transactions on Neural Systems and Rehabilitation Engineering.
“We were hoping that we could increase walking speed with exoskeleton assistance, but we were really surprised to find such a large improvement,” said Steve Collins, associate professor of mechanical engineering at Stanford and senior author of the paper. “Forty percent is huge.”
For this initial set of experiments, the participants were young, healthy adults. Given their impressive results, the researchers plan to run future tests with older adults and to look at other ways the exoskeleton design can be improved. They also hope to eventually create an exoskeleton that can work outside the lab, though that goal is still a ways off.
“My research mission is to understand the science of biomechanics and motor control behind human locomotion and apply that to enhance the physical performance of humans in daily life,” said Seungmoon Song, a postdoctoral fellow in mechanical engineering and lead author of the paper. “I think exoskeletons are very promising tools that could achieve that enhancement in physical quality of life.”
Walking in the loop
The ankle exoskeleton system tested in this research is an experimental emulator that serves as a testbed for trying out different designs. It has a frame that fastens around the upper shin and into an integrated running shoe that the participant wears. It is attached to large motors that sit beside the walking surface and pull a tether that runs up the length of the back of the exoskeleton. Controlled by an algorithm, the tether tugs the wearer’s heel upward, helping them point their toe down as they push off the ground.

Dr. Sabrina Coninx from Ruhr-Universität Bochum and Dr. Peter Stilwell from McGill University, Canada, have investigated how philosophical approaches can be used to think in new ways about pain and its management. The researchers advocate not merely reducing chronic pain management to searching and treating underlying physical changes but instead adopting an approach that focuses on the person as a whole. Their work was published online in the journal “Synthese” on 15 April 2021.
It is not currently possible to treat chronic pain effectively in many cases. This has encouraged researchers from various disciplines to consider new approaches to pain and its management over recent years. “Pain research and clinical practice do not take place in a vacuum, but instead involve implicit assumptions regarding what pain is and how it can be treated,” says Sabrina Coninx, research assistant at the Bochum research training group Situated Cognition. “Our aim is to shed light on these assumptions and discover how we can think in new ways about pain and its management with the help of philosophical approaches.” In their work, the authors develop a holistic, integrative and action-oriented approach.
Viewing patients as a whole
In specific terms, they suggest three things: firstly, addressing pain should involve more than just looking for and treating underlying physiological changes. A holistic approach places the focus on patients as a whole and creates space for their experiences, concerns, expectations and narratives. The influence of socio-cultural practices in the generation of chronic pain should also be taken into account. For example, pain patients are often initially encouraged to protect themselves from injury and avoid activity, which may be helpful in the beginning but can contribute to chronification in the long run.
Secondly, according to the researchers, chronic pain should be understood as a dynamic process in which many different factors interact in a non-linear way. The initial cause of pain, for instance, is not necessarily the cause of its chronification and also does not need to be the most crucial factor in treatment. The complex interaction of subjective experience, expectations, learned behavioural patterns, neural reorganisation, stigmatisation and other factors therefore needs to be considered.
Focus on action possibilities
Thirdly, according to Coninx and Stilwell, patients should be encouraged to interact with their environment and identify possibilities for action. This is based on the assumption that chronic pain fundamentally changes the way in which patients perceive themselves and their relationship with their environment. Pain treatment could therefore involve helping the patient to increasingly notice positively associated and personally meaningful options for action and view themselves as capable of taking action again. There is then less focus on the body as an obstacle, and instead the patients pay more attention to how they can overcome limitations.
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Materials provided by Ruhr-University Bochum. Note: Content may be edited for style and length.

Sugar is not just something we eat. On the contrary. Sugar is one of the most naturally occurring molecules, and all cells in the body are covered by a thick layer of sugar that protects the cells from bacteria and virus attacks. In fact, close to 80 per cent of all viruses and bacteria bind to the sugars on the outside of our cells.
Sugar is such an important element that scientists refer to it as the third building block of life — after DNA and protein. And last autumn, a group of researchers found that the spike protein in corona virus needs a particular sugar to bind to our cells efficiently.
Now the same group of researchers have completed a new study that further digs into the cell receptors to which sugars and thus bacteria and virus bind.
‘We have established how the sugars bind to and activate the so-called Siglec receptors that regulate immunity. These receptors play a major role, as they tell the immune system to decrease or increase activities. This is an important mechanism in connection with autoimmune diseases’, says the first author of the study, Postdoc Christian Büll from the Copenhagen Center for Glycomics (CCG) at the University of Copenhagen.
The unique sugar language
When the immune system receives wrong signals, it can lead to autoimmune diseases, which is when the immune system attacks itself. The Siglec receptors receive signals via the sialic acid sugar, a carbohydrate that typically closes the sugar chains on the surface of our cells. When Siglec receptors meet the right sugar chains, the immune system is told to dampen or activate.
‘As part of the new study, we have created a cell library that can be used to study how various sugars bind to and interact with receptors. We have done this by creating tens of thousands of cells each containing a bit of the unique sugar language, which enables us to distinguish them from one another and to study their individual effect and process. This knowledge can help us develop better treatment options in the future’, says Associate Professor Yoshiki Narimatsu from CCG, who also contributed to the study.
‘The surface of the cells in the library is the same as the one found on cells in their natural environment. This means that we can study the sugars in an environment with the natural occurrence of e.g. proteins and other sugars, and we can thus study the cells in the form in which virus and bacteria find them’, Yoshiki Narimatsu explains.
Important discovery for Alzheimer’s
Working on the new study, the researchers identified the sugars that bind to the specific receptor that plays a main role in the development of Alzheimer’s disease.
‘Our main finding concerns the Siglec-3 receptor. Mutations in the Siglec-3 receptor is already known to play a role in connection with Alzheimer’s, but we did not know what the receptor specifically binds to. Our method has now identified a potential natural sugar that binds specifically to the Siglec-3 receptor. This knowledge represents an important step forwards in understanding the genetic defects that cause a person to develop the disease’, says Christian Büll.
The creation of the sugar libraries was funded by the Lundbeck Foundation and the Danish National Research Foundation.

A new imaging technique developed by scientists at Columbia University Vagelos College of Physicians and Surgeons and St. Jude Children’s Research Hospital captures movies of receptors on the surface of living cells in unprecedented detail and could pave the way to a trove of new drugs.
The researchers used the technique to zoom in on individual receptor proteins on the surface of living cells to determine if the receptors work solo or come together to work as pairs. This work appeared in the April issue of Nature Methods.
“If two different receptors come together to form a dimer with distinctive function and pharmacology, this might allow for a new generation of drugs with greater specificity and reduced side effects,” says Jonathan Javitch, MD, PhD, the Lieber Professor of Experimental Therapeutics in Psychiatry at VP&S.
G-protein coupled receptors (GPCRs) are some of medicine’s most important molecules: About one-third of today’s drugs work by targeting a GPCR. The possibility that GPCRs form heterodimers — consisting of two different flavors of GPCR — is an especially exciting prospect for the development of better drugs.
“The potential of GPCR heterodimers for improved pharmacotherapies, including for disorders such as schizophrenia and depression, is exciting and has drawn us to the field,” Javitch says.
But for decades, scientists have hotly debated whether most GPCRs form dimers or work alone. Much of this impasse stemmed from the relatively poor spatial resolution of current techniques. Different GPCRs in a cell have been captured near each other, but it was unclear if the receptors were working together.
“The controversy over receptor dimerization has only grown fiercer with conflicting data from different labs using different methods,” Javitch says.
Using a new, more powerful technique based on single-molecule fluorescence resonance energy transfer (smFRET), Javitch and Scott C. Blanchard from St. Jude Children’s and Weill Cornell show that dimers can be tracked as they move on the cell surface and how long they last. This method takes advantage of a change in fluorescence that occurs when proteins, labeled with different fluorescent markers, are extremely close to each other. The resolution in this approach is more than 10 times greater than previous techniques.
This new and exciting technique entails multiple innovations in dyes, labeling technology, protein engineering, imaging, and software that enabled tracking of individual and coupled receptors.
Not only does this method detect GPCR dimers, it also allows, for the first time, a clear view of how receptors in a living cell change shape when activated. This will provide researchers a better understanding of how drugs can differentially impact the same receptors.
“With this method, we can now explore receptor interactions and activation mechanisms with unprecedented resolution, giving us an opportunity to investigate new therapeutic approaches,” Javitch says.
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Materials provided by Columbia University Irving Medical Center. Note: Content may be edited for style and length.

In their effort to understand the very earliest stages of life and how they can go wrong, scientists are confronted with ethical issues surrounding the use of human embryos. The use of animal embryos is also subject to restrictions rooted in ethical considerations. To overcome these limitations, scientists have been trying to recreate early embryos using stem cells.
One of the challenges in creating these so-called synthetic embryos is to generate all the cell types normally found in a young embryo before it implants into the wall of the uterus. Some of these cells eventually give rise to the placenta. Others become the amniotic sac in which the fetus grows. Both the placenta and the amniotic sac are crucial for the survival of the fetus, and defects in these embryo components are major causes of early pregnancy loss.
A group of scientists from Gladstone Institutes, the Center for iPS Cell Research and Application (CiRA) from Kyoto University, and the RIKEN Center for Biosystems Dynamics Research in Kobe, Japan, has now demonstrated the presence of precursors of the placenta and the amniotic sac in synthetic embryos they created from mouse stem cells.
“Our findings provide strong evidence that our system is a good model for studying the early, pre-implantation stages of embryo development,” says Kiichiro Tomoda, PhD, research investigator at the recently opened iPS Cell Research Center at Gladstone and first author of the study published in the journal Stem Cell Reports. “Using this model, we will be able to dissect the molecular events that take place during these early stages, and the signals that the different embryonic cells send to each other.”
Ultimately, this knowledge might help scientists develop strategies to decrease infertility due to early embryonic development gone awry.
The new findings could also shed light on a defining property of the earliest embryo cells that has been difficult to capture in the lab: their ability to produce all the cell types found in the embryo and, ultimately, the whole body. Scientists refer to this property as “totipotency.”
“Totipotency is a very unique and short-lived property of early embryonic cells,” says Cody Kime, PhD, an investigator at the RIKEN Center for Biosystems Dynamics Research and the study’s senior author.