Fishing for new source of proteoglycans, an important health food ingredient

Chondroitin sulfate proteoglycans (CSPGs), commonly obtained from salmon nasal cartilage, are a key ingredient of various health foods. As the popularity of health foods increases, scientists are searching for alternative sources of CSPGs. Now, researchers have analyzed the PGs and their CS structures in the head cartilage of 10 edible bony fishes, including sturgeons. Their findings point to several new fishes that can serve as alternatives to salmon as a source of CSPGs.
Aggrecan, a major component of proteoglycan (PG) having chondroitin sulfate (CS) in cartilaginous tissues, has become increasingly popular as an ingredient in health food. In fact, proteoglycans from salmon nasal cartilage demonstrate biological properties such as antiaging, inhibition of angiogenesis, and attenuation of inflammatory responses. Commercially available chondroitin sulfate proteoglycans (CSPGs) have only been prepared from salmon nasal cartilage. Although the head cartilage was found in other edible bony fishes, there is little information on the composition of core proteins and their CS structures in the head cartilage.
Now, in a new study published in the International Journal of Biology Macromolecules, a team of researchers led by Associate Professor Kyohei Higashi of Tokyo University of Science, and Dr. Naoshi Dohmae and Dr. Takehiro Suzuki of the RIKEN Center for Sustainable Resource Science tackles this question. “We found that composition of PGs and their CS structure in the skull of the Siberian sturgeon and Russian sturgeon were similar to that in the salmon nasal cartilage,” reports Dr. Higashi. The fishes for the study were provided by Mr. Atsuhi Nakamura from Miyazaki Prefectural Fisheries Research Institute. This study was made available online on March 23, 2022 and was published in Volume 208 of the journal on May 31, 2022.
All the fishes examined contained abundant CSPGs in the head cartilage. Comprehensive analysis of CS structure in PGs derived from 10 bony fishes revealed that the structure of CS derived from Perciformes were similar to that of CS derived from cartilage of terrestrial animals. On the other hand, the structure of CS from skull of sturgeons was similar to that of CS from salmon nasal cartilage. In addition, they also found that aggrecan, a major CSPG in the cartilaginous tissue, was conserved in 10 bony fishes. In fact, the aggrecan protein from LOC117428125 and LOC117964296 genes registered in the National Center for Biotechnology Information database was found to be abundant in the skull of sturgeons. Furthermore, compositions of other PGs, collagens, and matrix proteins in the skull of sturgeons were similar to that of salmon nasal cartilage.
Elaborating on the findings of this study, Dr. Kyohei Higashi says, “Head cartilage from bony fishes is an underutilized resource and is typically discarded after food processing. The PGs, especially from the sturgeon, are similar in CS structure to the salmon nasal cartilage, showing that the sturgeon has a lot of potential to be an alternative source of CSPGs for health food formulations.”
The researchers hope with further studies to evaluate the biological properties of sturgeon PG, bony fishes could become an important source for CS as well as PGs.
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Materials provided by Tokyo University of Science. Note: Content may be edited for style and length.

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Drug resistance molecule can spread though bacterial 'communities'

DNA molecules called plasmids — some of which protect bacteria from antibiotics — can spread rapidly through bacterial “communities” that are treated with antibiotics, new research shows.
Plasmids are found within bacterial cells, sometimes slowing bacterial reproduction — but they can carry genes that stop antibiotics from working (called antimicrobial resistance).
The new laboratory study, by the University of Exeter, found that a plasmid that benefits one or more species spreads not just through those species but to others in the community.
Bacterial communities exist both in the environment and in the “microbiome” of individual organisms including humans.
“Very often, antimicrobial resistance isn’t tied to the bacteria itself — it’s encoded in plasmids they carry, and can pass on,” said lead author Arthur Newbury, of the Environment and Sustainability Institute on Exeter’s Penryn Campus in Cornwall.
“Plasmids can jump between bacteria and, although most don’t cause antimicrobial resistance, those that do make the new host instantly resistant.

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Breathing to win: Scientists show importance of screening breathing patterns in athletic populations

Breathing patterns are an important indicator of an individual’s health. A healthy individual breathes naturally using primary respiratory muscles (e.g., diaphragm muscle) that produce a rhythmic observable movement of the upper rib cage, lower rib cage, and abdomen. This is known as the diaphragmatic breathing pattern, which has been associated with improvements in posture, core stability, and functional performance, as well as reductions in musculoskeletal injury, pain, and stress.
In contrast, individuals with altered or dysfunctional biomechanical breathing patterns are unable to contract their diaphragm to a desired extent and begin relying on accessory respiratory muscles to breathe. They display superior rib cage movement and shoulder elevation, reduced abdominal movements, and lateral rib cage expansion.
Previous research suggests a strong association between altered biomechanical breathing patterns and the development of musculoskeletal conditions, such as lower back pain, neck pain, chronic ankle instability, and temporomandibular joint disorders.
Superior physical performance and prevention of musculoskeletal injuries are crucial for athletes to deliver their best performance at competitive sports. Evidence from previous studies suggests that athletes with diaphragmatic breathing patterns display improved physical and psychological performance. But since athletes with altered breathing patterns might be at an enhanced risk of developing musculoskeletal injuries, identifying the prevalence of altered breathing patterns is of utmost importance to prevent them from developing injuries.
Now, a team of researchers led by Dr. Terada from Ritsumeikan University in Japan has conducted a novel study, published in The Journal of Strength and Conditioning Research, to examine the prevalence of dysfunctional and diaphragmatic breathing patterns in an athletic population, and determine the biomechanical dimensions of these breathing patterns.
The team tested 1933 competitive athletes from schools in Japan, across multiple sports and ages during 2017 and 2020, using a Hi-Lo test — a test that identifies an individual’s breathing pattern. Scores for the Hi-Lo test were determined based on the presence or absence of abdominal excursion, anterior-posterior chest expansion, superior rib cage migration and shoulder elevation. The team further classified these participants into thoracic-dominant and abdomen-only breathers based on the presence of abdominal excursion.
Findings indicate that an alarmingly high proportion (91%) of the athletes displayed dysfunctional breathing patterns, while only 9.4% of them displayed diaphragmatic breathing patterns. In fact, among athletes who played baseball, there was a greater percentage of diaphragmatic breathers than that among those who played tennis, basketball, badminton, and volleyball. This indicates that athletes’ breathing patterns vary depending on the type of sport they are involved in, since each sport has different energy demands and constraints.
Moreover, the team observed that the highest proportion of dysfunctional breathers were middle school student athletes, followed by elementary school student athletes, and high school student athletes. The proportion of collegiate athletes with dysfunctional breathing patterns was slightly lower in comparison.
Further, among the population identified as dysfunctional breathers, 61% of the athletes were found to be thoracic-dominant breathers, as compared to the 39% abdomen-only breathers.
These findings suggest an overall high prevalence of dysfunctional breathing patterns in the athletic population across age groups, which requires immediate addressing as an important sports-medicine issue.
When asked about the implications of these findings, Dr. Terada said “Clinicians need to consider screening breathing patterns and implementing corrective approaches targeted at specific components of dysfunctional breathing patterns. They should also consider evaluating sport-specific adaptations of breathing and implementing sport-specific breathing training protocols.”
The findings also emphasize the importance of the Hi-Lo test in recognizing the differences between sub-categories (thoracic-dominant and abdomen-only) of breathing patterns. An understanding of these breathing patterns can help develop individualized intervention plans. Dr. Terada says, “Incorporating diaphragm breathing exercises and techniques may have beneficial effects on restoring optimal recruitments and motor control patterns of respiratory muscles, improving the efficiency of the biomechanics of breathing and decreasing psychological stress in athletes with dysfunctional breathing patterns.”

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3D in a snap: Next generation system for imaging organoids

Biomedical researchers develop and use organoids as a tool for studying human development and disease. These little lab-grown cultures mimic human organs and provide a sharp view of tissue development, drug interaction, and other biochemical functions, offering an innovative approach to personalized medicine.
“Getting detailed 3D images of these miniature models of organs, and getting a good look at how they change under different conditions or stimulation, can tell us a lot about how the body works,” said Shuichi Takayama, professor and Price Gilbert Jr. Chair in Regenerative Engineering and Medicine in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University. “It can tell us how diseases progress, or how mechanical forces and certain drugs may change or affect cellular behavior.”
The trick is in getting those detailed images. Fluorescence 3D microscopy has helped transform the study of organoids at the cellular and subcellular levels — though with a few drawbacks. Conventional methods are time consuming and don’t adequately capture the fast, dynamic, sometimes unpredictable cellular and tissue processes of these model systems.
Now, a team of Georgia Tech researchers has built a better system to quickly produce high-resolution 3D images in real time, providing a quantitative analysis of organoids. Led by Coulter BME Assistant Professor Shu Jia, their custom-built microscope can reconstruct a comprehensive 3D representation with a single camera image. They described their system in the journal Biosensors and Bioelectronics.
Jia’s new system builds on his lab’s growing body of work in next-generation imaging systems. Conventional 3D imaging technologies rely on time-consuming, redundant scanning-based techniques, which can result in damaged cells and compromised images. Jia’s team has pioneered a faster light-field system that provides greater resolution and minimizes photo damage. Their new system does all of that and more.
“This latest system is novel because it is entirely custom-built for imaging at the tissue and animal scale,” said Jia, who earlier this year received a CAREER award from the National Science Foundation. “We built everything from scratch on an optical table.”
Adding a hybrid point-spread function to the new system allows researchers to capture scanning-free recordings of intact organoids in all of their dynamic glory in milliseconds instead of minutes or even hours using conventional methods. With a single camera image, Jia’s system can reconstruct a time-lapse observation of the 3D volume of the samples.
“We can look — cell by cell — throughout the entire organoid, in high spatial and time resolution, and see from multiple angles what happens as a result of an external perturbation, or a response to a specific drug, or any change in the overall environment,” Jia said.
He said the imaging systems coming out of his lab have the potential to transform conventional 3D microscopy.
“Because this is a custom-built system, it’s very flexible and adaptive,” he added. “It works with organoids, but similarly, it can work with animal models. I think we can extend this method to different areas of research. There are a number of potential collaborations we are exploring.”
This research was supported by the National Institutes of Health (grant Nos. R35GM124846 and AI116482) and the National Science Foundation (grant Nos. EFMA1830941 and 2145235). Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of any funding agency.
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Materials provided by Georgia Institute of Technology. Original written by Jerry Grillo. Note: Content may be edited for style and length.

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Inappropriate antibiotics for nonhospitalized kids cost US at least $74 million

Antibiotics inappropriately prescribed to nonhospitalized children resulted in at least $74 million in excess health-care costs in the U.S. in 2017, according to a new study from Washington University School of Medicine in St. Louis and The Pew Charitable Trusts.
Children who were prescribed unneeded or unsuitable antibiotics in outpatient settings, such as doctors’ offices and urgent care centers, also were up to eight times more likely to develop complications such as diarrhea and skin rashes than children who were treated according to standard medical guidelines.
The findings, published May 26 in JAMA Network Open, highlight the need to better manage antibiotic use outside hospital settings.
“Inappropriate prescribing of antibiotics is unfortunately very common and leads to adverse drug events and millions of dollars in avoidable health-care costs,” said lead author Anne Mobley Butler, PhD, an assistant professor of medicine in the Division of Infectious Diseases at Washington University. “Sometimes parents think that the worst that could happen is that the antibiotic just won’t help their child. But antibiotics are not harmless — they can cause adverse drug events. Clinicians needs to insure that antibiotics are only used in the way that is most likely to benefit the patient.”
Antibiotics kill bacteria, not viruses, but doctors still frequently prescribe antibiotics for viral infections. For bacterial infections, antibiotics can be helpful, but it is important to choose an appropriate antibiotic agent, and doctors do not always follow guideline recommendations. A previous study suggests that about 29% of antibiotic prescriptions for nonhospitalized children nationwide are inappropriate.
On a population level, antibiotic use drives the development of antibiotic-resistant bacteria. Such bacteria cause difficult-to-treat infections that lead to 35,000 deaths in the U.S. each year. But less is known about the individual health risks and economic costs associated with inappropriate antibiotic use.

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Harnessing the immune system to treat traumatic brain injury in mice

A therapeutic method for harnessing the body’s immune system to protect against brain damage is published today by researchers from the Babraham Institute’s Immunology research programme. The collaboration between Professor Adrian Liston (Babraham Institute) and Professor Matthew Holt (VIB and KU Leuven; i3S-University of Porto) has produced a targeted delivery system for boosting the numbers of specialised anti-inflammatory immune cells specifically within the brain to restrict brain inflammation and damage. Their brain-specific delivery system protected against brain cell death following brain injury, stroke and in a model of multiple sclerosis. The research is published today in the journal Nature Immunology.
Traumatic brain injury, like that caused during a car accident or a fall, is a significant cause of death worldwide and can cause long-lasting cognitive impairment and dementia in people who survive. A leading cause of this cognitive impairment is the inflammatory response to the injury, with swelling of the brain causing permanent damage. While inflammation in other parts of the body can be addressed therapeutically, but in the brain it is problematic due to the presence of the blood-brain barrier, which prevents common anti-inflammatory molecules from getting to the site of trauma.
Prof. Liston, a senior group leader in the Babraham Institute’s Immunology programme, explained their approach: “Our bodies have their own anti-inflammatory response, regulatory T cells, which have the ability to sense inflammation and produce a cocktail of natural anti-inflammatories. Unfortunately there are very few of these regulatory T cells in the brain, so they are overwhelmed by the inflammation following an injury. We sought to design a new therapeutic to boost the population of regulatory T cells in the brain, so that they could manage inflammation and reduce the damage caused by traumatic injury.”
The research team found that regulatory T cell numbers were low in the brain because of a limited supply of the crucial survival molecule interleukin 2, also known as IL2. Levels of IL2 are low in the brain compared to the rest of the body as it can’t pass the blood-brain barrier.
Together the team devised a new therapeutic approach that allows more IL2 to be made by brain cells, thereby creating the conditions needed by regulatory T cells to survive. A ‘gene delivery’ system based on an engineered adeno-associated viral vector (AAV) was used: this system can actually cross an intact blood brain barrier and deliver the DNA needed for the brain to produce more IL2 production.
Commenting on the work, Prof. Holt, from VIB and KU Leuven, said: “For years, the blood-brain barrier has seemed like an insurmountable hurdle to the efficient delivery of biologics to the brain. Our work, using the latest in viral vector technology, proves that this is no longer the case; in fact, it is possible that under certain circumstances, the blood-brain barrier may actually prove to be therapeutically beneficial, serving to prevent ‘leak’ of therapeutics into the rest of the body.”
The new therapeutic designed by the research teams was able to boost the levels of the survival molecule IL2 in the brain, up to the same levels found in the blood. This allowed the number of regulatory T cells to build up in the brain, up to 10-fold higher than normal. To test the efficacy of the treatment in a mouse model that closely resembles traumatic brain injury accidents, mice were given carefully controlled brain impacts and then treated with the IL-2 gene delivery system. The scientists found that the treatment was effective at reducing the amount of brain damage following the injury, assessed by comparing both the loss of brain tissue and the ability of the mice to perform in cognitive tests.
Lead author, Dr Lidia Yshii, Associate Professor at KU Leuven, explained: “Seeing the brains of the mice after the first experiment was a ‘eureka moment’ — we could immediately see that the treatment reduced the size of the injury lesion.”
Recognising the wider potential of a drug capable of controlling brain inflammation, the researchers also tested the effectiveness of the approach in experimental mouse models of multiple sclerosis and stroke. In the model of multiple sclerosis, treating mice during the early symptoms prevented severe paralysis and allowed the mice to recover faster. In a model of stroke, mice treated with the IL2 gene delivery system after a primary stroke were partially protected from secondary strokes occurring two weeks later. In a follow-up study, still undergoing peer review, the research team also demonstrated that the treatment was effective at preventing cognitive decline in ageing mice.
“By understanding and manipulating the immune response in the brain, we were able to develop a gene delivery system for IL2 as a potential treatment for neuroinflammation. With tens of millions of people affected every year, and few treatment options, this has real potential to help people in need. We hope that this system will soon enter clinical trials, essential to test whether the treatment also works in patients.” said Prof. Liston.
Dr Ed Needham, a neurocritical care consultant at Addenbrooke’s Hospital who was not a part of the study, commented on the clinical relevance of these results: “There is an urgent clinical need to develop treatments which can prevent secondary injury that occurs after a traumatic brain injury. Importantly these treatments have to be safe for use in critically unwell patients who are at high risk of life-threatening infections. Current anti-inflammatory drugs act on the whole immune system, and may therefore increase patients’ susceptibility to such infections. The exciting progress in this study is that, not only can the treatment successfully reduce the brain damage caused by inflammation, but it can do so without affecting the rest of the body’s immune system, thereby preserving the natural defences needed to survive critical illness.”

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Radio 1's Adele Roberts reveals life with a stoma

Last October, the Radio 1 DJ Adele Roberts announced she’d been diagnosed with bowel cancer. She’s been through intense treatment, and now wears a stoma bag as her bowel recovers. This month, Adele – and her stoma – are on the front cover of “Women’s Health”, as she continues to break down the stigma surrounding her diagnosis. BBC Breakfast followed Adele and her partner Kate, you can watch their story here.

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Gut bacteria can make blood pressure medication less effective

A new study from The University of Toledo College of Medicine and Life Sciences has shown gut bacteria can reduce the effectiveness of certain blood pressure drugs.
The research, published this month in the journal Hypertension, offers the first clues to what has been an elusive mystery — why do some people not respond well to medication?
“High blood pressure is often called a silent killer because it doesn’t usually cause symptoms. However, there is a big population of individuals who know they have hypertension but still cannot get it under control, even though they’re taking blood pressure drugs,” said Dr. Tao Yang, an assistant professor in the Department of Physiology and Pharmacology and the study’s first and lead author. “Addressing this is of huge clinical importance.”
Hypertension, or high blood pressure, is a major risk factor for heart disease and stroke, two of the leading causes of death in America. It’s also one of the most common chronic conditions in the United States, with nearly half of U.S. adults considered hypertensive under current guidelines.
Among those with high blood pressure, an estimated 20% have what’s known as resistant hypertension, meaning their blood pressure remains high despite aggressive treatment.
“The only thing doctors can really do in these patients is adding or switching medications and increasing the dose with the hope they can find something that works,” Yang said. “Until now, we haven’t had any clear indication what the mechanism is for resistant hypertension. Our research could provide a first step toward identifying new ways to effectively overcome treatment-resistant hypertension.”
In recent years researchers have more intently examined the link between an individual’s blood pressure readings and the unique collection of bacteria that lives in their gut.

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A nanoparticle and inhibitor trigger the immune system, outsmarting brain cancer

Scientistsat the University of Michigan Rogel Cancer Center were optimistic when they identified a small molecule that blocked a key pathway in brain tumors. But there was a problem: How to get the inhibitor through the bloodstream and into the brain to reach the tumor.
In collaboration with multiple labs, the teams fabricated a nanoparticle to contain the inhibitor, and the results were even better than expected.
Not only did the nanoparticles deliver the inhibitor to the tumor in mouse models, where the drug successfully turned on the immune system to eliminate the cancer, but the process triggered immune memory so that a reintroduced tumor was also eliminated — a sign that this potential new approach could not only treat brain tumors but prevent or delay recurrences.
“No one could get this molecule into the brain. It’s really a huge milestone. Outcomes for patients with glioma have not improved for the last 30 years,” said Maria G. Castro, Ph.D., R.C. Schneider Collegiate Professor of Neurosurgery at Michigan Medicine. Castro is the senior author of the study, published in ACS Nano.
“Despite survival gains in many cancer types, glioma remains stubbornly challenging, with only 5% of patients living five years after their diagnosis,” said study author Pedro R. Lowenstein, M.D., Ph.D., Richard C. Schneider Collegiate Professor of Neurosurgery at Michigan Medicine.
Gliomas are often resistant to traditional therapies, and the environment inside the tumor suppresses the immune system, rendering new immune-based therapies ineffective. Add to that the challenge of passing the blood brain barrier, and it becomes even more difficult to deliver effective treatments to these tumors.

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More young people begin recreational cannabis use illegally in states that legalize it

Once a state legalizes recreational cannabis, residents are more likely to start using it, including those too young to do so legally, report researchers at University of California San Diego. The findings, published online in the May 26, 2022 issue of Addiction, counter claims that legalization does not increase cannabis use, particularly among youth.
The observational study tracked 6,925 youths and 14,938 adults using data from the Population Assessment of Tobacco and Health in the United States (PATH). Study authors found that young people, ages 12 to 20, were more likely to become cannabis users in states that legalize recreational use than in states that have not legalized the drug. An increased likelihood of use was also documented in adults.
According to a 2020 Natural Survey on Drug Use and Health, 17.9 percent of people aged 12 or older (approximately 49.6 million persons) reported using cannabis in the past 12 months.
Subjects in the study lived in four states that have legalized recreational cannabis use in recent years (California, Massachusetts, Nevada and Maine), 11 states that allow medical cannabis use and 17 states that prohibit all cannabis use.
The authors said using PATH data made the study the first to estimate age-level changes in a nationally representative longitudinal cohort. The study also has a much larger sample size than previous efforts.
“Our findings provide useful information to policymakers and public health practitioners interested in understanding the consequences of legalizing recreational cannabis,” said principal investigator Yuyan Shi, PhD, associate professor at the Herbert Wertheim School of Public Health and Human Longevity Science at UC San Diego. “It’s especially concerning that increased cannabis use occurs among young people because of the detrimental health effects associated with cannabis use at a young age, including impaired respiratory function, cardiovascular disease and adverse effects on mental health.”
Co-authors include: Christian Gunadi, UC San Diego; and Bin Zhu, UC San Diego and Southern University of Science and Technology, China.
Funding for this research came, in part, from the National Institute on Drug Abuse (R01DA042290, R01DA049730).
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Materials provided by University of California – San Diego. Original written by Yadira Galindo. Note: Content may be edited for style and length.

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