Sat. Sep 21st, 2019

264 APCNO REPORT 14 JUN 2019

264APCNO31MAY2019

In this issue:

  1. Avocados, as a substitution for carbohydrates, can suppress hunger without adding calories
  2. Broccoli sprout compound may restore brain chemistry imbalance linked to schizophrenia
  3. Montmorency tart cherries may provide benefits for adults with metabolic syndrome
  4. Newly identified bacteria-killing protein needs vitamin A to work
  5. Glucosamine supplements may be linked to lower risk of cardiovascular disease
  6. Strawberry tree honey inhibits cell proliferation in colon cancer lines
  7. Natural compound found in broccoli reawakens the function of potent tumor suppressor
  8. Bacteria in fermented food signal the human immune system, explaining health benefits
  9. Cranberries join forces with antibiotics to fight bacteria
  10. Healthy fat hidden in dirt may fend off anxiety disorders
  11. Salty diet reduces tumor growth by tackling immune cells
  12. Vitamin D could help cancer patients live longer
  13. Tart cherry shown to decrease joint pain, sore muscles in some breast cancer patients
  14. Researchers warn: junk food could be responsible for the food allergy epidemic
  15. Low vitamin K levels linked to mobility limitation and disability in older adults

NEWS RELEASE 8-MAY-2019

Avocados, as a substitution for carbohydrates, can suppress hunger without adding calories

New study at Illinois Tech finds meals that include fresh avocado can significantly suppress hunger and increase meal satisfaction

ILLINOIS INSTITUTE OF TECHNOLOGY

Chicago-May 7, 2019 – A new study released by the Center for Nutrition Research at Illinois Institute of Technology suggests that meals that include fresh avocado as a substitute for refined carbohydrates can significantly suppress hunger and increase meal satisfaction in overweight and obese adults.

As rates of obesity in the United States continue to rise, the findings from Illinois Tech suggest that simple dietary changes can have an important impact on managing hunger and aiding metabolic control.

The new research, published in the peer-reviewed journal Nutrients, assessed the underlying physiological effects of including whole and half fresh Hass avocados on hunger, fullness, and how satisfied subjects felt over a six-hour period. Researchers evaluated these effects in 31 overweight and obese adults in a randomized three-arm crossover clinical trial. These dietary changes were also shown to limit insulin and blood glucose excursions, further reducing the risk of diabetes and cardiovascular disease by adding healthy fats and fibers into a regular daily diet.

“For years, fats have been targeted as the main cause of obesity, and now carbohydrates have come under scrutiny for their role in appetite regulation and weight control,” said Britt Burton-Freeman, Ph.D., director of the Center for Nutrition Research at Illinois Tech. “There is no ‘one size fits all’ solution when it comes to optimal meal composition for managing appetite. However, understanding the relationship between food chemistry and its physiological effects in different populations can reveal opportunities for addressing appetite control and reducing rates of obesity, putting us a step closer to personalized dietary recommendations.”

The research found that meals including avocado not only resulted in a significant reduction in hunger and an increase in how satisfied participants felt, but also found that an intestinal hormone called PYY was an important messenger of the physiological response.

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The study and research team was led by Britt Burton-Freeman, Ph.D., of the Center for Nutrition Research, Institute for Food Safety and Health, Illinois Institute of Technology and was supported by the Hass Avocado Board. The Institute for Food Safety and Health is a one-of-a-kind applied food science and nutrition research consortium comprised of Illinois Tech faculty and staff, the U.S. Food and Drug Administration, and the food industry. In collaboration with the FDA, the institute provides stakeholders with the opportunity to develop and exchange knowledge, experience, and expertise in the areas of food safety, food defense, food processing, and nutrition.

NEWS RELEASE 8-MAY-2019

Broccoli sprout compound may restore brain chemistry imbalance linked to schizophrenia

JOHNS HOPKINS MEDICINE

In a series of recently published studies using animals and people, Johns Hopkins Medicine researchers say they have further characterized a set of chemical imbalances in the brains of people with schizophrenia related to the chemical glutamate. And they figured out how to tweak the level using a compound derived from broccoli sprouts.

They say the results advance the hope that supplementing with broccoli sprout extract, which contains high levels of the chemical sulforaphane, may someday provide a way to lower the doses of traditional antipsychotic medicines needed to manage schizophrenia symptoms, thus reducing unwanted side effects of the medicines.

“It’s possible that future studies could show sulforaphane to be a safe supplement to give people at risk of developing schizophrenia as a way to prevent, delay or blunt the onset of symptoms,” adds Akira Sawa, M.D., Ph.D., professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine and director of the Johns Hopkins Schizophrenia Center.

Schizophrenia is marked by hallucinations, delusions and disordered thinking, feeling, behavior, perception and speaking. Drugs used to treat schizophrenia don’t work completely for everyone, and they can cause a variety of undesirable side effects, including metabolic problems increasing cardiovascular risk, involuntary movements, restlessness, stiffness and “the shakes.”

In a study described in the Jan. 9 edition of the journal JAMA Psychiatry, the researchers looked for differences in brain metabolism between people with schizophrenia and healthy controls. They recruited 81 people from the Johns Hopkins Schizophrenia Center within 24 months of their first psychosis episode, which can be a characteristic symptom of schizophrenia, as well as 91 healthy controls from the community. The participants were an average of 22 years old, and 58% were men.

The researchers used a powerful magnet to measure and compare five regions in the brain between the people with and without psychosis. A computer analysis of 7-Tesla magnetic resonance spectroscopy (MRS) data identified individual chemical metabolites and their quantities.

The researchers found on average 4% significantly lower levels of the brain chemical glutamate in the anterior cingulate cortex region of the brain in people with psychosis compared to healthy people.

Glutamate is known for its role in sending messages between brain cells, and has been linked to depression and schizophrenia, so these findings added to evidence that glutamate levels have a role in schizophrenia.

Additionally, the researchers found a significant reduction of 3% of the chemical glutathione in the brain’s anterior cingulate cortex and 8% in the thalamus. Glutathione is made of three smaller molecules, and one of them is glutamate.

Next, the researchers asked how glutamate might be managed in the brain and whether that management is faulty in disease. They first looked at how it’s stored. Because glutamate is a building block of glutathione, the researchers wondered if the brain might use glutathione as a way to store extra glutamate. And if so, the researchers questioned if they could use known drugs to shift this balance to either release glutamate from storage when there isn’t enough, or send it into storage if there is too much.

In another study, described in the Feb. 12 issue of the journal PNAS, the team used the drug L-Buthionine sulfoximine in rat brain cells to block an enzyme that turns glutamate into glutathione, allowing it to be used up. The researchers found that theses nerves were more excited and fired faster, which means they were sending more messages to other brain cells. The researchers say shifting the balance this way is akin to shifting the brain cells to a pattern similar to one found in the brains of people with schizophrenia. Next, the researchers wanted to see if they could do the opposite and shift the balance to get more glutamate stored in the form of glutathione. They used the chemical sulforaphane found in broccoli sprouts, which is known to turn on a gene that makes more of the enzyme that sticks glutamate with another molecule to make glutathione. When they treated rat brain cells with glutathione, it slowed the speed at which the nerve cells fired, meaning they were sending fewer messages. The researchers say this pushed the brain cells to behave less like the pattern found in brains with schizophrenia.

“We are thinking of glutathione as glutamate stored in a gas tank,” says Thomas Sedlak, M.D., Ph.D., assistant professor of psychiatry and behavioral sciences. “If you have a bigger gas tank, you have more leeway on how far you can drive, but as soon as you take the gas out of the tank it’s burned up quickly. We can think of those with schizophrenia as having a smaller gas tank.”

Because sulforaphane changed the glutamate imbalance in the rat brains and affected how messages were transmitted between the rat brain cells, the researchers wanted to test whether sulforaphane could change glutathione levels in healthy people’s brains and see if this could eventually be a strategy for people with mental disorders. For their study, published in April 2018 in Molecular Neuropsychiatry, the researchers recruited nine healthy volunteers (four women, five men) to take two capsules with 100 micromoles daily of sulforaphane in the form of broccoli sprout extract for seven days.

The volunteers reported that a few of them were gassy and some had stomach upset when eating the capsules on an empty stomach, but overall the sulforaphane was relatively well tolerated.

The researchers used MRS again to monitor three brain regions for glutathione levels in the healthy volunteers before and after taking sulforaphane. They found that after seven days, there was about a 30% increase in average glutathione levels in the subjects’ brains. For example, in the hippocampus, glutathione levels rose an average of 0.27 millimolar from a baseline of 1.1 millimolar after seven days of taking sulforaphane.

The scientists say further research is needed to learn whether sulforaphane can safely reduce symptoms of psychosis or hallucinations in people with schizophrenia. They would need to determine an optimal dose and see how long people must take it to observe an effect. The researchers caution that their studies don’t justify or demonstrate the value of using commercially available sulforaphane supplements to treat or prevent schizophrenia, and patients should consult their physicians before trying any kind of over-the-counter supplement. Versions of sulforaphane supplementsare sold in health food stores and at vitamin counters, and aren’t regulated by the U.S. Food and Drug Administration.

“For people predisposed to heart disease, we know that changes in diet and exercise can help stave off the disease, but there isn’t anything like that for severe mental disorders yet,” says Sedlak. “We are hoping that we will one day make some mental illness preventable to a certain extent.”

Sulforaphane is found in a variety of cruciferous vegetables, and was first identified as a “chemoprotective” substance decades ago by Paul Talalay and Jed Fahey at Johns Hopkins.

According to the World Health Organization, schizophrenia affects about 21 million people worldwide.

NEWS RELEASE 7-MAY-2019

Montmorency tart cherries may provide benefits for adults with metabolic syndrome

Suggests new pilot study

LANSING, Mich. May 7, 2019 – Montmorency tart cherries reduced systolic blood pressure, insulin levels and insulin concentrations in adults with metabolic syndrome participating in a small pilot study published in the Journal of Functional Foods. [1]

While previous studies on Montmorency tart cherries have explored individual aspects of metabolic syndrome – such as blood pressure and triglycerides – this is the first study to examine the full cluster of conditions that comprise metabolic syndrome, including insulin resistance, hypertension and central obesity, or belly fat. Nearly 35% of U.S. adults are estimated to have metabolic syndrome, which significantly increases the risk of cardiovascular disease and type 2 diabetes.

“Our most noteworthy cardiovascular response observed in the study was the significant reduction in systolic blood pressure for the first two hours after consumption,” said lead author Terun Desai, from the School of Life and Medical Sciences at the University of Hertfordshire in Hatfield, UK. “The unique composition of tart cherries, including the synergistic influence of anthocyanins, other polyphenols, and fiber may be a factor.”

Study Methodology

A group of 11 men and women, ages 37-61, participated in this randomized, placebo-controlled crossover trial. All participants met at least three of the five criteria for metabolic syndrome (waist circumference > 35 inches for women or 40 inches for men, high or borderline high triglyceride levels, low levels of HDL, high blood pressure, and high fasting blood sugar).

During the 6-week study, on three different occasions, each separated by a 14-day washout period, participants consumed either Montmorency tart cherry juice (30 ml of juice concentrate mixed with 100 ml of water), Montmorency tart cherry capsules (10 capsules to match the anthocyanin content of the juice with 130 ml water) or a placebo drink (30 ml of a fruit-flavored syrup mixed with 100 ml of water). The juice contained the equivalent of about 90-110 whole tart cherries and the capsules were made from about 100 whole tart cherries. The placebo drink was matched to the tart cherry juice for calories, taste and visual appearance using maltodextrin (a flavorless carbohydrate), citric acid and red and black food coloring.

Each testing day began between 7:00-10:00 a.m., with participants instructed to fast overnight for at least 10 hours. Height, weight, waist circumference and markers of heart and metabolic health (including arterial stiffness, blood pressure, heart rate, cardiac output, stroke volume, mean arterial pressure, total peripheral resistance, resting metabolic rate, glucose and insulin levels, insulin resistance/sensitivity and blood lipids) were measured at baseline. With the exception of height, weight and waist circumference, these tests were repeated at regular intervals over 5 hours after the drink or capsules were consumed.

Results

The U.K. researchers found Montmorency tart cherry juice led to a significant, clinically-relevant reduction in systolic blood pressure when compared to the placebo 2 hours after consumption, and Montmorency tart cherry juice and Montmorency tart cherry capsules both lowered insulin levels significantly more than the placebo at 1 hour and 3 hours, respectively. Arterial stiffness was also improved 2 hours after consumption of Montmorency tart cherry juice compared to the placebo, however the significance of this finding is unclear as other indicators of vascular stiffness were not improved. No significant differences were found for the other outcomes examined. The results are preliminary and more research is needed with a larger sample size.

“Global rates of metabolic syndrome are on the rise and the results of the present study suggest Montmorency tart cherries, in juice or capsule form, could exert beneficial effects for adults with this condition when incorporated into an overall healthy diet,” said Desai.

The researchers also demonstrated that, while certain effects differed at certain points in time, overall responses between Montmorency tart cherry capsules and Montmorency tart cherry juice were not statistically different. This refutes their original hypothesis that capsules may be superior to juice due to an increased bioavailability of anthocyanins. Given this study’s acute nature, longer-term research to enhance clinical relevance is warranted.

NEWS RELEASE 14-MAY-2019

Newly identified bacteria-killing protein needs vitamin A to work

DALLAS – May 14, 2019 – People who have inadequate vitamin A in their diets are more susceptible to skin infection, yet how that vitamin affects skin immunity has been unclear. In a study published today, UT Southwestern researchers shed some light on that mystery by identifying a previously unknown bacteria-killing protein on the epidermis that requires the vitamin to work.

The researchers found that one protein in the resistin-like molecule (RELM) family – RELMα – acts as an antibiotic to rapidly kill bacteria. Both RELMα, which is made by mice, and the corresponding human RELM family protein, called resistin, are stimulated by dietary vitamin A.

“RELMα is the first example of an antimicrobial protein that requires dietary vitamin A for its bacterial killing activity. This finding gives us an important clue about how the skin defends itself against infection, and how skin defense is regulated by the diet,” said Dr. Lora Hooper, Chair of Immunology and corresponding author on the study published in Cell Host & Microbe.

Dermatologists use synthetic vitamin A, called retinoid, to treat acne, psoriasis, and other skin conditions, although how those drugs work has long been a mystery.

“The skin is the largest organ of the human body and is tasked with defending us against infection,” said Dr. Tamia Harris-Tryon, Assistant Professor of Dermatology and Immunology.

“If the skin immune system breaks down, infection results. Skin infections, from bacteria such as Streptococcus, are among the most common reasons people come to the emergency room,” added Dr. Harris-Tryon, a physician-scientist who completed postdoctoral training in the Hooper lab.

Dr. Hooper is well known for her research on the commensal or “good” bacteria that inhabit the gut – where they aid in digestion and infection control.

The team’s experiments in human tissue and mice illuminate a previously unappreciated link between diet and innate immunity of the skin, suggesting why vitamin A derivatives are effective treatments for skin disease, said Dr. Hooper, a Howard Hughes Medical Institute Investigator who is also a UTSW Professor of Immunology and Microbiology with an additional appointment in the Center for the Genetics of Host Defense. Dr. Hooper holds the Jonathan W. Uhr, M.D. Distinguished Chair in Immunology and is a Nancy Cain and Jeffrey A. Marcus Scholar in Medical Research, in Honor of Dr. Bill S. Vowell.

In addition to identifying RELMα’s unique feature – its requirement for dietary vitamin A to kill bacteria – the team showed that mice fed a diet deficient in vitamin A made no RELMα. The researchers also found that mice missing RELMα were more susceptible to infection and had different bacterial species on their skin compared with typical mice.

Dr. Harris-Tryon added, “Considering how often retinoids are used in dermatology, the implications of our findings are potentially vast. The skin is an important interface between us and the environment and must defend us against infection and inflammation. We are just beginning to understand how bacteria and the microbiome (the term for the population of bacteria living with us) impact skin diseases such as psoriasis and acne. Our work helps to define the molecules that the skin uses to create a healthy relationship between the microbiome and us, the hosts.”

To study how the microbiome impacts immunity, the researchers used Dr. Hooper’s colony of germ-free mice – mice raised from birth without exposure to germs – and identified genes that are turned on when such mice are exposed to bacteria.

“When the skin encounters bacteria, cells respond by making molecules that help defend the skin against infection,” she explained, adding that scientists at the National Institutes of Health (NIH) collaborated on the study.

The researchers included some caveats.

“This study gives us a better understanding of how diet impacts the ability of the skin to defend itself against bacterial infection – but more research will be needed to determine how these findings will impact patients with inflammatory skin diseases such as acne and psoriasis,” said Dr. Harris-Tryon, who earned her M.D.-Ph.D. at Johns Hopkins University.

NEWS RELEASE 14-MAY-2019

Glucosamine supplements may be linked to lower risk of cardiovascular disease

Findings suggest possible preventive role, but further trials needed to test this theory

BMJ

Regular use of glucosamine supplements may be related to a lower risk of cardiovascular disease (CVD) events, suggests an analysis of data from the UK Biobank study, published in The BMJ today.

The findings suggest that glucosamine may have benefits in preventing CVD events, such as coronary heart disease and stroke, and further clinical trials are needed to test this theory, say the researchers.

Glucosamine is a popular dietary supplement used to relieve osteoarthritis and joint pain. While its effectiveness on joint pain continues to be debated, emerging evidence suggests that glucosamine may have a role in preventing cardiovascular disease and reducing mortality. However, conclusive evidence is still lacking

So to explore these potential associations further, researchers led by Professor Lu Qi at Tulane University in New Orleans drew on data from the UK Biobank – a large population based study of more than half a million British men and women.

Their analysis included 466,039 participants without CVD, who completed a questionnaire on supplement use, including glucosamine.

Death certificates and hospital records were then used to monitor CVD events, including CVD death, coronary heart disease (CHD), and stroke, over an average seven-year follow up period.

Overall, almost one in five (19.3%) participants reported glucosamine use at the start of the study.

The researchers found that glucosamine use was associated with a 15% lower risk of total CVD events, and a 9% to 22% lower risk of CHD, stroke, and CVD death compared with no use.

These favourable associations remained after taking account of traditional risk factors, including age, sex, weight (BMI), ethnicity, lifestyle, diet, medication and other supplement use.

The association between glucosamine use and CHD was also stronger in current smokers (37% lower risk) compared with never (12%) and former smokers (18%).

Several mechanisms may explain these results, say the authors. For example, regular use of glucosamine has been linked to a reduction in levels of C-reactive protein (CRP), a chemical associated with inflammation. This may also help to explain the stronger association among smokers, who have higher levels of inflammation and higher risk of CVD than non-smokers.

In addition, previous data suggest that glucosamine may mimic a low carbohydrate diet, which has been inversely associated with the development of CVD.

Despite the large sample size, this is an observational study, and as such, can’t establish cause, and the researchers point to some limitations, such as lack of information on dose, duration, and side effects of glucosamine use.

Regular glucosamine use may also be a marker for a healthy lifestyle, they add, but this is unlikely to have affected the results.

As such, they conclude that “habitual use of glucosamine supplements to relieve osteoarthritis pain might also be related to lower risks of CVD events. Further clinical trials are warranted to test this hypothesis.”

NEWS RELEASE 20-MAY-2019

Strawberry tree honey inhibits cell proliferation in colon cancer lines

FECYT – SPANISH FOUNDATION FOR SCIENCE AND TECHNOLOGY

CREDIT: AFRIN, S. ET AL.

Spanish and Italian researchers have proven that when honey from strawberry trees, a product typical of Mediterranean areas, is added to colon cancer cells grown in the laboratory, cell proliferation is stopped. The authors hope that these promising results and the anti-tumour potential of this food will be confirmed in in vivo models.

The honey extracted from the flowers of the strawberry tree (Arbutus unedo) is appreciated in the beekeeping sector for its organoleptic characteristics, especially for its strong bitter taste and dark colour. Now, scientists from the universities of Vigo and Granada (Spain) and from the Polytechnic University of Marche (Italy) have analysed for the first time the potential of this Mediterranean product to fight colon cancer.

The results, published in the Journal of Functional Foods, show that strawberry tree honey is capable of inhibiting the proliferation of tumour cells cultivated in laboratory plates – more specifically, those of a line of human colon adenocarcinoma (HCT-116) and another with metastatic characteristics (LoVo), widely used to investigate this type of tumour.

“Treatment with honey stops the tumour cells cycle by regulating some genes (cyclin D1, CDK2, p27Kip…); it inhibits cell migration, reduces the ability to form colonies and induces apoptosis or programmed cell death through the modulation of other key genes (p53, caspase-3, c-PARP) and various apoptotic factors,” says Maurizio Battino, coordinator of the research.

“It also suppresses the receptor of the epidermal growth factor called EGFR/HER2 and its signalling pathways, which could be an attractive target in cancer therapies because of their important role in the processes of cell survival and proliferation, as well as in those of apoptosis and metastasis.”

The cytotoxicity and anti-tumour effects of strawberry tree honey in relation to colon cancer lines increased with the amount and time of treatment. This led to other relevant results, such as the reduction of some transcription factors, the inhibition of the activity of certain enzymes and the decrease of mitochondrial respiration and glycolysis of tumour cells.

“None of these effects was observed when honey was applied to healthy cell lines,” the authors point out, noting the anticarcinogenic potential of this natural product, but insisting on the need for new studies with colon cancer in vivo models to confirm its chemopreventive effects.

“With these data it is not yet possible to speak of a cure or safe prevention of colorectal cancer thanks to strawberry tree honey,” emphasizes Battino, who adds: “This work constitutes a starting point in the effort to evaluate its possible biological and anti-cancer effects and indicates the main molecular mechanisms through which it exerts its effect, reinforcing the interest in the study and production of this Mediterranean foodstuff.”

“It is one more piece of evidence that a healthy, balanced and natural diet can provide bioactive compounds with possible interesting effects on the control and development of diseases as critical as this type of cancer,” concludes the researcher.

NEWS RELEASE 16-MAY-2019

Natural compound found in broccoli reawakens the function of potent tumor suppressor

Finding offers potential novel approach to cancer treatment and prevention

BETH ISRAEL DEACONESS MEDICAL CENTER

BOSTON – Your mother was right; broccoli is good for you. Long associated with decreased risk of cancer, broccoli and other cruciferous vegetables – the family of plants that also includes cauliflower, cabbage, collard greens, Brussels sprouts and kale – contain a molecule that inactivates a gene known to play a role in a variety of common human cancers. In a new paper published today in Science, researchers, led by Pier Paolo Pandolfi, MD, PhD, Director of the Cancer Center and Cancer Research Institute at Beth Israel Deaconess Medical Center, demonstrate that targeting the gene, known as WWP1, with the ingredient found in broccoli suppressed tumor growth in cancer-prone lab animals.

“We found a new important player that drives a pathway critical to the development of cancer, an enzyme that can be inhibited with a natural compound found in broccoli and other cruciferous vegetables,” said Pandolfi. “This pathway emerges not only as a regulator for tumor growth control, but also as an Achilles’ heel we can target with therapeutic options.”

A well-known and potent tumor suppressive gene, PTEN is one of the most frequently mutated, deleted, down-regulated or silenced tumor suppressor genes in human cancers. Certain inherited PTEN mutations can cause syndromes characterized by cancer susceptibility and developmental defects. But because complete loss of the gene triggers an irreversible and potent failsafe mechanism that halts proliferation of cancer cells, both copies of the gene (humans have two copies of each gene; one from each parent) are rarely affected. Instead, tumor cells exhibit lower levels of PTEN, raising the question whether restoring PTEN activity to normal levels in the cancer setting can unleash the gene’s tumor suppressive activity.

To find out, Pandolfi and colleagues identified the molecules and compounds regulating PTEN function and activation. Carrying out a series of experiments in cancer prone mice and human cells, the team revealed that a gene called WWP1 – which is also known to play a role in the development of cancer – produces an enzyme that inhibits PTEN’s tumor suppressive activity. How to disable this PTEN kryptonite? By analyzing the enzyme’s physical shape, the research team’s chemists recognized that a small molecule – formally named indole-3-carbinol (I3C), an ingredient in broccoli and its relatives – could be the key to quelling the cancer causing effects of WWP1.

When Pandolfi and colleagues tested this idea by administering I3C to cancer prone lab animals, the scientists found that the naturally occurring ingredient in broccoli inactivated WWP1, releasing the brakes on the PTEN’s tumor suppressive power.

But don’t head to the farmer’s market just yet; first author Yu-Ru Lee, PhD, a member of the Pandolfi lab, notes you’d have to eat nearly 6 pounds of Brussels sprouts a day – and uncooked ones at that – to reap their potential anti-cancer benefit. That’s why the Pandolfi team is seeking other ways to leverage this new knowledge. The team plans to further study the function of WWP1 with the ultimate goal of developing more potent WWP1 inhibitors.

“Either genetic or pharmacological inactivation of WWP1 with either CRISPR technology or I3C could restore PTEN function and further unleash its tumor suppressive activity,” said Pandolfi. “These findings pave the way toward a long-sought tumor suppressor reactivation approach to cancer treatment.”

NEWS RELEASE 23-MAY-2019

Bacteria in fermented food signal the human immune system, explaining health benefits

Ability to detect bacteria may have enabled human ancestors to eat not-so-fresh food

PLOS

Researchers have discovered that humans and great apes possess a receptor on their cells that detects metabolites from bacteria commonly found in fermented foods and triggers movement of immune cells. Claudia Stäubert of the University of Leipzig and colleagues report these findings in a new study published 23rd May in PLOS Genetics.

Consuming lactic acid bacteria – the kind that turn milk into yogurt and cabbage into sauerkraut – can offer many health benefits, but scientists still don’t understand, on a molecular level, why it is helpful to ingest these bacteria and how that affects our immune system. Now, Stäubert and her colleagues have found one way that lactic acid bacteria interact with our bodies. Initially the researchers were investigating proteins on the surface of cells called hydroxycarboxylic acid (HCA) receptors. Most animals have only two types of this receptor but humans and great apes have three. The researchers discovered that a metabolite produced by lactic acid bacteria, D-phenyllactic acid, binds strongly to the third HCA receptor, signalling the immune system their presence. The researchers propose that the third HCA receptor arose in a common ancestor of humans and great apes, and enabled them to consume foods that are starting to decay, such as fruits picked up from the ground.

The study yields new insights into the evolutionary dynamics between microbes and their human hosts and opens new research directions for understanding the multiple positive effects of eating fermented foods. “We are convinced that this receptor very likely mediates some beneficial and anti-inflammatory effects of lactic acid bacteria in humans,” stated author Claudia Stäubert. “That is why we believe it could serve as a potential drug target to treat inflammatory diseases.”

Future studies may reveal the details of how D-phenyllactic acid impacts the immune system, and whether the metabolite also affects fat cells, which also carry the third HCA receptor on their surfaces.

NEWS RELEASE 28-MAY-2019

Cranberries join forces with antibiotics to fight bacteria

Research conducted at McGill University and INRS has found that a cranberry extract makes bacteria more sensitive to antibiotics, a promising avenue for limiting resistance to these important drugs

MCGILL UNIVERSITY

The global spread of antibiotic resistance is undermining decades of progress in fighting bacterial infections. Due to the overuse of antibiotics in medicine and agriculture, we are on the cusp of returning to a pre-antibiotic era in which minor infections can once again become deadly. Therefore, countering the fall in antibiotic efficacy by improving the effectiveness of currently available antibiotics is a crucial goal.

Cranberries are highly sought after for their tangy taste and the antioxidants they contain, but a new study published in the journal Advanced Science provides evidence that they could also help in the fight against bacteria. When treated with molecules derived from cranberries, pathogenic bacteria become more sensitive to lower doses of antibiotics. What’s more, the bacteria don’t develop resistance to the antibiotics, according to the findings by researchers at McGill University and INRS (Institut national de la recherche scientifique) in Montreal.

Given the popular belief that drinking cranberry juice is helpful against urinary tract infections, the researchers sought to find out more about the berry’s molecular properties by treating various bacteria with a cranberry extract. The bacteria selected for study were those responsible for urinary tract infections, pneumonia, and gastro-enteritis (Proteus mirabilis, Pseudomonas aeruginosa, and Escherichia coli).

“Normally when we treat bacteria with an antibiotic in the lab, the bacteria eventually acquire resistance over time,” said McGill chemical engineering professor Nathalie Tufenkji, lead author of the study. “But when we simultaneously treated the bacteria with an antibiotic and the cranberry extract, no resistance developed. We were very surprised by this, and we see it as an important opportunity.”

Analyses showed that the cranberry extract increases bacterial sensitivity to antibiotics by acting in two ways. First, it makes the bacterial cell wall more permeable to the antibiotic, and second, it interferes with the mechanism used by the bacteria to pump out the antibiotic. Consequently, the antibiotic penetrates more easily, and the bacteria have a harder time getting rid of it, which explains why the drug is effective at lower doses.

“These are really exciting results,” said coauthor Éric Déziel, a professor of microbiology at INRS. “The activity is generated by molecules called proanthocyanidins. There are several different kinds of proanthocyanidins, and they may work together to deliver this outcome. We’ll need to do more research to determine which ones are most active in synergy with the antibiotic.”

After confirming the activity of the cranberry molecules on bacterial culture, the researchers tested to determine whether the pattern persisted in a preliminary animal model: infected insects. Since the synergistic effect of the extract and the antibiotic was also observed in the insects, further experiments will be conducted to clearly identify the active molecules.

If the results are confirmed in animals, certain classes of antibiotics subject to high levels of resistance could be made useful again by using cranberry extract to boost their potential.

“We are eager to pursue this research further,” Tufenkji said. “Our hope is to reduce the doses of antibiotics required in human and veterinary medicine as part of efforts to combat antibiotic resistance.”

NEWS RELEASE 29-MAY-2019

Healthy fat hidden in dirt may fend off anxiety disorders

Lipid discovered in soil-dwelling bacteria helps explain ‘hygiene hypothesis’

UNIVERSITY OF COLORADO AT BOULDER

Thirty years after scientists coined the term “hygiene hypothesis” to suggest that increased exposure to microorganisms could benefit health, University of Colorado Boulder researchers have identified an anti-inflammatory fat in a soil-dwelling bacterium that may be responsible.

The discovery, published Monday in the journal Psychopharmacology, may at least partly explain how the bacterium, Mycobacterium vaccae, quells stress-related disorders. It also brings the researchers one step closer to developing a microbe-based “stress vaccine.”

“We think there is a special sauce driving the protective effects in this bacterium, and this fat is one of the main ingredients in that special sauce,” said senior author and Integrative Physiology Professor Christopher Lowry.

British scientist David Strachan first proposed the controversial “hygiene hypothesis” in 1989, suggesting that in our modern, sterile world, lack of exposure to microorganisms in childhood was leading to impaired immune systems and higher rates of allergies and asthma.

Researchers have since refined that theory, suggesting that it is not lack of exposure to disease-causing germs at play, but rather to “old friends” – beneficial microbes in soil and the environment – and that mental health is also impacted.

“The idea is that as humans have moved away from farms and an agricultural or hunter-gatherer existence into cities, we have lost contact with organisms that served to regulate our immune system and suppress inappropriate inflammation,” said Lowry, who prefers the phrases ‘old friends hypothesis’ or ‘farm effect.’ “That has put us at higher risk for inflammatory disease and stress-related psychiatric disorders.”

Lowry has published numerous studies demonstrating a link between exposure to healthy bacteria and mental health.

One showed that children raised in a rural environment, surrounded by animals and bacteria-laden dust, grow up to have more stress-resilient immune systems and may be at lower risk of mental illness than pet-free city dwellers.

Others have shown that when a particular bacterium, Mycobacterium vaccae, is injected into rodents, it alters the animals’ behavior in a way similar to that of antidepressants and has long-lasting anti-inflammatory effects on the brain. Studies suggest exaggerated inflammation boosts risk of trauma- and stressor-related disorders, such as posttraumatic stress disorder (PTSD).

One recent Lowry-authored study, published in the Proceedings of the National Academy of Sciences in 2017, showed that injections of M. vaccae prior to a stressful event could prevent a “PTSD-like” syndrome in mice, fending off stress-induced colitis and making the animals act less anxious when stressed again later.

“We knew it worked, but we didn’t know why,” said Lowry. “This new paper helps clarify that.”

For the new study, Lowry and his team identified, isolated and chemically synthesized a novel lipid, or fatty acid, called 10(Z)-hexadecenoic acid found in Mycobacterium vaccae and used next-generation sequencing techniques to study how it interacted with macrophages, or immune cells, when the cells were stimulated.

They discovered that inside cells, the lipid acted like a key in a lock, binding to a specific receptor, peroxisome proliferator-activated receptor (PPAR), and inhibiting a host of key pathways which drive inflammation. They also found that when cells were pre-treated with the lipid they were more resistant to inflammation when stimulated.

“It seems that these bacteria we co-evolved with have a trick up their sleeve,” said Lowry. “When they get taken up by immune cells, they release these lipids that bind to this receptor and shut off the inflammatory cascade.”

Lowry has long envisioned developing a “stress vaccine” from M. vaccae, which could be given to first responders, soldiers and others in high-stress jobs to help them fend off the psychological damage of stress.

“This is a huge step forward for us because it identifies an active component of the bacteria and the receptor for this active component in the host,” he said.

Simply knowing the mechanism of action by which M. vaccae reaps benefits could boost confidence in it as a potential therapeutic. And if further studies show the novel fat alone has therapeutic effects, that molecule could become a target for drug development, he said.

Overall, the study offers further proof that our “old friends” have a lot to offer.

“This is just one strain of one species of one type of bacterium that is found in the soil but there are millions of other strains in soils,” Lowry said. “We are just beginning to see the tip of the iceberg in terms of identifying the mechanisms through which they have evolved to keep us healthy. It should inspire awe in all of us.”

NEWS RELEASE 5-JUN-2019

Salty diet reduces tumor growth by tackling immune cells

A study by an international research team led by Professor Markus Kleinewietfeld (VIB-UHasselt) shows that high salt intake inhibits tumor growth in mice. The effect seems to be due to a change in function of certain immune cells which play a critical role in cancer immunity. The further exploration of this finding might be beneficial for improving anti-cancer immunotherapies.

Salt impacts experimental tumor models

High salt intake is a known risk factor for high blood pressure and cardiovascular diseases. Recent research has also indicated that too much salt may impact autoimmunity. Studies have shown that a high salt diet could change the immune cell balance towards a more aggressive state and worsen autoimmunity. Interestingly, these shifts in the immune cell balance, though detrimental in autoimmune conditions, could be in theory useful in anti-cancer immune therapies to improve immune attacks against tumor cells.

An international research team led by Prof. Kleinewietfeld that included Prof. Sven Brandau (University of Duisburg-Essen, Germany), Dr. Thomas Kammertöns (Charite & MDC-Berlin, Germany) and Prof. Jo Van Ginderachter (VIB-VUB) have now investigated the impact of high salt intake on tumor growth in mice. They found that a high salt diet inhibited tumor growth in two independent mouse models. The research team further found that this effect seemed to be related to a change in the functions of certain immune cells, so called myeloid-derived suppressor cells (MDSCs). MDSCs are believed to hinder other immune cells to efficiently attack and eliminate tumor cells.

Immune cells changing function

When the researchers mimicked a salty environment in cell culture, they observed a functional change in MDSCs. The cells were less capable to inhibit other immune cells. A similar modulatory effect of high salt conditions on MDSCs was observed with cells isolated from human cancer patients. Moreover, if these cells were depleted, the effect of a high salt diet on tumor growth in mice was undone.

MDSCs are suspected to be an important mechanism that prevents an efficient immune attack against tumors in anti-cancer immunotherapies. The underlying molecular mechanism that blocks the function of these cells could therefore have therapeutic potential. However, since high salt intake is suspected to be a risk factor for gastric cancer in humans, the findings of this study and molecular mechanisms behind them must be carefully analyzed in future studies.

Prof. Kleinewietfeld (VIB-UHasselt): “The findings are highly interesting, and we were surprised to see such an effect on tumor growth just by increasing the salt in the diet. However, future studies are needed to fully understand the effect and the detailed underlying molecular mechanisms behind to judge its therapeutic potential for anti-cancer immunotherapies.

NEWS RELEASE 3-JUN-2019

Vitamin D could help cancer patients live longer

EAST LANSING, Mich. – Michigan State University physicians have found that vitamin D, if taken for at least three years, could help cancer patients live longer.

The findings suggest that the vitamin carries significant benefits other than just contributing to healthy bones and were presented at the American Society of Clinical Oncology annual meeting on June 3, 2019.

In the United States, cancer is the second leading cause of death, according to the Centers for Disease Control and Prevention.

“Vitamin D had a significant effect on lowering the risk of death among those with cancer, but unfortunately it didn’t show any proof that it could protect against getting cancer,” said Tarek Haykal, a lead author on the study and an internal medicine resident physician at Michigan State University and Hurley Medical Center in Flint, Michigan.

The researchers looked at data related to disease prevention from more than 79,000 patients in multiple studies that randomly compared the use of vitamin D to a placebo over at least a three-year period. Haykal and his team zeroed in on any information that involved cancer incidence and mortality.

“The difference in the mortality rate between the vitamin D and placebo groups was statistically significant enough that it showed just how important it might be among the cancer population,” Haykal said.

While these findings show promise, Haykal cautioned that the exact amount of the vitamin to take and what levels are needed in the blood are still unknown. He also said that it’s unclear how much longer vitamin D extends lifespan and why it has this result.

“There are still many questions and more research is needed,” Haykal said. “All we can say is that at least three years of taking the supplement is required to see any effect.”

Results show enough promise, however, that Haykal would like to see more doctors, especially oncologists, prescribe vitamin D to patients in general.

“We know it carries benefits with minimal side effects, he said. “There’s plenty of potential here.”

NEWS RELEASE 10-JUN-2019

Tart cherry shown to decrease joint pain, sore muscles in some breast cancer patients

MARSHALL UNIVERSITY JOAN C. EDWARDS SCHOOL OF MEDICINE

HUNTINGTON, W.Va. – Tart cherry reduces the musculoskeletal effects of aromatase inhibitors in patients with non-metastatic breast cancer, according to new findings from a clinical trial by researchers at Marshall University Joan C. Edwards School of Medicine and Edwards Comprehensive Cancer Center.

Aromatase inhibitors (AIs) are a standard treatment for hormone receptor-positive breast cancer in postmenopausal women. These agents can help prevent recurrence of the disease by inhibiting the action of aromatase, an enzyme responsible for conversion of androgens to estrogens. About half of patients who take AIs also suffer from joint and muscle pain known as aromatase inhibitor induced arthralgia, which, at times, can be debilitating and cause patients to not complete their treatments.

This randomized, double-blind trial compared the consumption of 1 ounce of tart cherry concentrate in 8 ounces of water daily for six weeks with a placebo group in women with stage 1, 2 or 3 non-metastatic breast cancer. A total of 60 patients were enrolled throughout the course of the clinical trial, conducted May 2016 to August 2018.

Patients documented their pain intensity at the start of the trial, weekly and at study completion. Patients who completed the trial recorded a 34.7% mean decrease in pain compared to 1.4% in the placebo group.

“The flavonoids and anthocyanins in tart cherry have anti-inflammatory properties and may be playing a role in reducing the side effects of joint pain and muscles aches, although etiology of aromatase-induced arthralgias remain unclear at this time,” said principal investigator Maria Tria Tirona, M.D., professor of hematology-oncology at the Marshall University Joan C. Edwards School of Medicine and director of medical oncology at Edwards Comprehensive Cancer Center. “There was a statistically significant difference in the pain levels experienced by patients in the group that received the tart cherry concentrate compared to the placebo group.”

NEWS RELEASE 7-JUN-2019

Researchers warn: junk food could be responsible for the food allergy epidemic

SPINK HEALTH

(Glasgow, 8 June, 2019) Experts at the 52nd Annual Meeting of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition are today presenting the results of a study that show higher levels of advanced glycation end products (AGEs), found in abundance in junk food, are associated with food allergy in children [1].

Researchers from the University of Naples ‘Federico II’ observed three groups of children aged between 6-12 years old (61 children in total): those with food allergies, those with respiratory allergies, and healthy controls. The study revealed a significant correlation between subcutaneous levels of advanced glycation end products (AGEs) and junk food consumption, and further, that children with food allergies presented with higher levels of subcutaneous levels of AGEs than those children with respiratory allergies or no allergies at all. In addition, the research team found compelling evidence relating to the mechanism of action elicited by AGEs in determining food allergy.

AGEs are proteins or lipids that become glycated after exposure to sugars [2] and are present at high levels in junk foods – deriving from sugars, processed foods, microwaved foods and roasted or barbequed meats. AGEs are already known to play a role in the development and progression of different oxidative-based diseases including diabetes, atherosclerosis (where plaque builds up inside the arteries), and neurological disorders [3] but this is the first time an association has been found between AGEs and food allergy.

While firm statistics on global food allergy prevalence are lacking, there is growing evidence that incidence is on the increase, especially amongst young children, and prevalence is reported to be as high as 10% in some countries [4,5,6]. Similarly, over recent decades there has been a dramatic increase in the consumption of highly-processed foods [7] (which are known to contain higher levels of AGEs), and highly-processed foods have been reported as comprising up to 50% of total daily energy intake in European countries [8].

Commenting on the research, principal investigator Roberto Berni Canani said:

“As of yet, existing hypotheses and models of food allergy do not adequately explain the dramatic increase observed in the last years – so dietary AGEs may be the missing link. Our study certainly supports this hypothesis, we now need further research to confirm it. If this link is confirmed, it will strengthen the case for national governments to enhance public health interventions to restrict junk food consumption in children.”

Isabel Proaño, Director of Policy and Communications at the European Federation of Allergy and Airways Diseases Patients’ Associations (EFA) added:

“These new findings show there are still many environmental and dietary issues affecting our health and wellbeing. Healthcare professionals and patients do not have all of the important information to face a disease that dramatically impacts their quality of life, and industrialised food processing and labelling gaps will not help them. We call on the public health authorities to enable better prevention and care of food allergy.”

NEWS RELEASE 13-JUN-2019

Low vitamin K levels linked to mobility limitation and disability in older adults

TUFTS UNIVERSITY, HEALTH SCIENCES CAMPUS

BOSTON (June 13, 2019)–Low levels of circulating vitamin K are linked to increased risk of mobility limitation and disability in older adults, identifying a new factor to consider for maintaining mobility and independence in older age, according to a study led by researchers at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University.

The study, published online in May in advance of print in the Journal of Gerontology: Medical Sciences, is the first to evaluate the association between biomarkers of vitamin K status and the onset of mobility limitation and disability in older adults.

“Because of our growing population of older people, it’s important for us to understand the variety of risk factors for mobility disability,” said Kyla Shea, first and corresponding author and a nutrition scientist in the Vitamin K Laboratory at the Jean Mayer USDA Human Nutrition Research Center on Aging (HNRCA) at Tufts University.

“Low vitamin K status has been associated with the onset of chronic diseases that lead to disability, but the work to understand this connection is in its infancy. Here, we’re building on previous studies that found that low levels of circulating vitamin K are associated with slower gait speed and a higher risk of osteoarthritis,” she continued.

The new study examined two biomarkers: circulating levels of vitamin K (phylloquinone) and a functional measure of vitamin K (plasma ucMGP). Using participant data from the Health, Aging, and Body Composition Study (Health ABC), the study found that older adults with low levels of circulating vitamin K were more likely to develop mobility limitation and disability. The other biomarker, plasma ucMGP, did not show clear associations with mobility limitation and disability.

Specifically, older adults with low circulating vitamin K levels were nearly 1.5 times more likely to develop mobility limitation and nearly twice as likely to develop mobility disability compared to those with sufficient levels. This was true for both men and women.

“The connection we saw with low levels of circulating vitamin K further supports vitamin K’s association with mobility disability,” said senior author Sarah Booth, a vitamin K and nutrition researcher, and director of the HNRCA. “Although the two biomarkers we looked at are known to reflect vitamin K status, biomarker levels can also be affected by additional known or unknown factors. Further experiments to understand the mechanisms of biomarkers and vitamin K and their role in mobility are needed.”

The study used data from 635 men and 688 women ages 70-79 years old, approximately 40 percent of whom were black, who participated in Health ABC. In Health ABC, mobility was assessed every six months for six to ten years through annual clinic visits and phone interviews in the intervening time. For the present analysis, the researchers defined mobility limitation as two consecutive semi-annual reports of having any amount of difficulty either with walking a quarter of a mile or climbing 10 steps without resting, and mobility disability as two consecutive semi-annual reports of having a lot of difficulty or inability to walk or climb the same amount.

Circulating vitamin K levels reflect the amount of vitamin K in the diet. The best food sources of vitamin K include leafy greens such as spinach, kale and broccoli and some dairy products. For an average adult, one cup of raw spinach provides 145 micrograms (mcg) of vitamin K1, or 181 percent of the Daily Value; one cup of raw kale provides 113 mcg, or 141 percent; and half of a cup of chopped boiled broccoli provides 110 mcg, or 138 percent.

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