257 CNO REPORT 28 AUG 2018

Est. 257CNO31JUL2018

25clip_image0027CNO28AUG2018

CNO Report # 257

Release Date:  28 AUG 2018

Draft Report Compiled by

Ralph Turchiano

http://www.clinicalnews.org

 

 

 

In This Issue:

1.       An orange a day keeps macular degeneration away: 15-year study

2.       Products of omega-3 fatty acid metabolism may have anticancer effects, study shows

3.       Fish consumption may prolong life

4.       Cannabinoids may have a vast array of anti-cancer effects

5.       Beef jerky and other processed meats associated with manic episodes

6.       Scientists reverse aging-associated skin wrinkles and hair loss in a mouse model

7.       New study: Omega-3s help keep kids out of trouble

8.       Common painkillers triple harmful side effects in dementia

9.       Depression linked to low blood levels of acetyl-L-carnitine

10.   Active substance raises hopes of curing hepatitis E

11.   Low plasma levels of omega-3 fatty acids associated with preterm birth

12.   Mushrooms of the Far East hold promise for the anti-cancer therapy

13.   Soy diets might increase women’s bone strength

14.   Chemicals found in vegetables prevent colon cancer in mice

15.   Higher omega-3 index associated with better brain function in children

16.   Clay to fight bacteria in wounds: An old practice may be a new solution

17.   Could vitamin B3 treat acute kidney injury?

18.   Consuming milk at breakfast lowers blood glucose throughout the day

19.   Maple leaf extract could nip skin wrinkles in the bud

 

Public Release: 12-Jul-2018

An orange a day keeps macular degeneration away: 15-year study

A new study has shown that people who regularly eat oranges are less likely to develop macular degeneration than people who do not eat oranges

Westmead Institute for Medical Research

that people who regularly eat oranges are less likely to develop macular degeneration than people who do not eat oranges.

Researchers at the Westmead Institute for Medical Research interviewed more than 2,000 Australian adults aged over 50 and followed them over a 15-year period.

The research showed that people who ate at least one serving of oranges every day had more than a 60% reduced risk of developing late macular degeneration 15 years later.

Lead Researcher Associate Professor Bamini Gopinath from the University of Sydney said the data showed that flavonoids in oranges appear to help prevent against the eye disease.

“Essentially we found that people who eat at least one serve of orange every day have a reduced risk of developing macular degeneration compared with people who never eat oranges,” she said.

“Even eating an orange once a week seems to offer significant benefits.

“The data shows that flavonoids found in oranges appear to help protect against the disease.”

Associate Professor Gopinath said that until now most research has focused on the effects of common nutrients such as vitamins C, E and A on the eyes.

 

“Our research is different because we focused on the relationship between flavonoids and macular degeneration.

“Flavonoids are powerful antioxidants found in almost all fruits and vegetables, and they have important anti-inflammatory benefits for the immune system.

“We examined common foods that contain flavonoids such as tea, apples, red wine and oranges.

“Significantly, the data did not show a relationship between other food sources protecting the eyes against the disease,” she said.

One in seven Australians over 50 have some signs of macular degeneration. Age is the strongest known risk factor and the disease is more likely to occur after the age of 50.

There is currently no cure for the disease.

The research compiled data from the Blue Mountains Eye Study, a benchmark population-based study that started in 1992.

It is one of the world’s largest epidemiology studies, measuring diet and lifestyle factors against health outcomes and a range of chronic diseases.

“Our research aims to understand why eye diseases occur, as well as the genetic and environmental conditions that may threaten vision,” Associate Professor Gopinath concluded.

 

Public Release: 13-Jul-2018

Products of omega-3 fatty acid metabolism may have anticancer effects, study shows

University of Illinois at Urbana-Champaign

CHAMPAIGN, Ill. — A class of molecules formed when the body metabolizes omega-3 fatty acids could inhibit cancer’s growth and spread, University of Illinois researchers report in a new study in mice. The molecules, called endocannabinoids, are made naturally by the body and have similar properties to cannabinoids found in marijuana – but without the psychotropic effects.

In mice with tumors of osteosarcoma – a bone cancer that is notoriously painful and difficult to treat – endocannabinoids slowed the growth of tumors and blood vessels, inhibited the cancer cells from migrating and caused cancer cell death. The results were published in the Journal of Medicinal Chemistry.

“We have a built-in endocannabinoid system which is anti-inflammatory and pain-reducing. Now we see it is also anti-cancer, stopping the cells from proliferating or migrating,” said study leader Aditi Das, a professor of comparative biosciences and an affiliate of biochemistry at Illinois. “These molecules could address multiple problems: cancer, inflammation and pain.”

In 2017, the Illinois team identified a new group of omega-3 fatty-acid metabolites called endocannabinoid epoxides, or EDP-EAs. They found that these molecules had anti-inflammatory properties and targeted the same receptor in the body that cannabis does.

Since cannabis has been shown to have some anti-cancer properties, in the new study the researchers investigated whether EDP-EAs also affect cancer cells. They found that in mice with osteosarcoma tumors that metastasized to their lungs, there was an 80 percent increase in naturally occurring EDP-EAs in cancerous lung tissues over the lungs of healthy mice.

“The dramatic increase indicated that these molecules were doing something to the cancer – but we didn’t know if it was harmful or good,” Das said. “We asked, are they trying to stop the cancer, or facilitating it? So we studied the individual properties and saw that they are working against the cancer in several ways.”

The researchers found that in higher concentrations, EDP-EAs did kill cancer cells, but not as effectively as other chemotherapeutic drugs on the market. However, the compounds also combated the osteosarcoma in other ways: They slowed tumor growth by inhibiting new blood vessels from forming to supply the tumor with nutrients, they prevented interactions between the cells, and most significantly, they appeared to stop cancerous cells from migrating.

“The major cause of death from cancer is driven by the spread of tumor cells, which requires migration of cells,” said study coauthor Timothy Fan, a professor of veterinary clinical medicine and veterinary oncology. “As such, therapies that have the potential to impede cell migration also could be useful for slowing down or inhibiting metastases.”

The researchers isolated the most potent of the molecules and are working to develop derivatives that bind better to the cannabinoid receptor, which is plentiful on the surface on cancer cells.

“Dietary consumption of omega-3 fatty acids can lead to the formation of these substances in the body and may have some beneficial effects. However, if you have cancer, you want something concentrated and fast acting,” Das said. “That’s where the endocannabinoid epoxide derivatives come into play – you could make a concentrated dose of the exact compound that’s most effective against the cancer. You could also mix this with other drugs such as chemotherapies.”

Next, the researchers plan to perform preclinical studies in dogs, since dogs develop osteosarcoma spontaneously, similarly to humans. They also plan to study the effects of EDP-EAs derived from omega-3 fatty acids in other cancer types.

“Particular cancers that might be most interesting to study would be solid tumors or carcinomas, which tend to spread and cause pain within the skeleton. Some of the most common tumors that behave this way are breast, prostate, and lung carcinomas, and we can certainly explore these tumors in the future,” said Fan, who is also a member of the Carle Illinois College of Medicine, the Cancer Center at Illinois and the Carl R. Woese Institute for Genomic Biology.

Public Release: 18-Jul-2018

Fish consumption may prolong life

Wiley

Consumption of fish and long-chain omega-3 fatty acids was associated with lower risks of early death in a Journal of Internal Medicine study.

In the study of 240,729 men and 180,580 women who were followed for 16 years, 54,230 men and 30,882 women died. Higher fish and long-chain omega-3 fatty acid intakes were significantly associated with lower total mortality. Comparing the highest with lowest quintiles of fish intake, men had 9% lower total mortality, 10% lower cardiovascular disease mortality, 6% lower cancer mortality, 20% lower respiratory disease mortality, and 37% lower chronic liver disease mortality, while women had 8% lower total mortality, 10% lower cardiovascular disease mortality, and 38% lower Alzheimer’s disease mortality.

Fried fish consumption was not related to mortality in men, whereas it was associated with increased risks of mortality from all causes, cardiovascular disease, and respiratory disease in women. Long-chain omega-3 fatty acid intake was associated with 15% and 18% lower cardiovascular disease mortality in men and women, respectively, when comparing the highest and lowest quintiles.

Public Release: 18-Jul-2018

Cannabinoids may have a vast array of anti-cancer effects

Wiley

Previous research has shown that cannabinoids can help lessen side effects of anti-cancer therapies. Now a new British Journal of Pharmacology review has examined their potential for the direct treatment of cancer.

Phytocannabinoids are the most notable type of cannabinoid, and they occur naturally in the cannabis plant. Studies have shown that cannabinoids may stop cancer cells from dividing and invading normal tissue, and they may block the blood supply to tumors. Some studies also indicate that cannabinoids may enhance the body’s immune response against the growth and spread of tumors.

“There is still a need for additional anti-cancer drugs. In this context accumulating data from preclinical models suggest that cannabinoids elicit anti-cancer effects on several levels of cancer progression,” said author Prof. Burkhard Hinz, of Rostock University Medical Center, in?Germany. “Clinical studies are now urgently needed to investigate the impact of cannabinoids on cancer growth and progression in patients.”

Peer Reviewed Review Human

Public Release: 18-Jul-2018

Beef jerky and other processed meats associated with manic episodes

Johns Hopkins Medicine

An analysis of more than 1,000 people with and without psychiatric disorders has shown that nitrates–chemicals used to cure meats such as beef jerky, salami, hot dogs and other processed meat snacks–may contribute to mania, an abnormal mood state. Mania is characterized by hyperactivity, euphoria and insomnia.

The findings of the Johns Hopkins Medicine study, which was not designed to determine cause and effect, were published July 18 in Molecular Psychiatry. Specifically, it found that people hospitalized for an episode of mania had more than three times the odds of having ever eaten nitrate-cured meats than people without a history of a serious psychiatric disorder.

Experiments in rats by the same researchers showed mania-like hyperactivity after just a few weeks on diets with added nitrates.

While a number of genetic and other risk factors have been linked to the manic episodes that characterize bipolar disorder and may occur in other psychiatric conditions, those factors have been unable to explain the cause of these mental illnesses, and researchers are increasingly looking for environmental factors, such as diet, that may play a role.

The researchers say that their new study adds to evidence that certain diets and potentially the amounts and types of bacteria in the gut may contribute to mania and other disorders that affect the brain.

“Future work on this association could lead to dietary interventions to help reduce the risk of manic episodes in those who have bipolar disorder or who are otherwise vulnerable to mania,” says lead author Robert Yolken, M.D., the Theodore and Vada Stanley Distinguished Professor of Neurovirology in Pediatrics at the Johns Hopkins University School of Medicine.

Mania, a state of elevated mood, arousal and energy that lasts weeks to months, is generally seen in people with bipolar disorder, but can also occur in those with schizoaffective disorder. Manic states can lead to dangerous risk-taking behavior and can include delusional thinking, and most of those affected experience multiple hospitalizations in the course of their psychiatric illness.

Bipolar disorder affects an estimated 1 to 3 percent of the population of the United States and costs an estimated $25 billion a year in direct health care costs, according to a study in the Journal of Affective Disorders.

Yolken, trained as an infectious disease expert, was originally interested in whether exposure to infections such as viruses transmitted through food might be linked to any psychiatric conditions. Between 2007 and 2017, as part of an ongoing study, he and colleagues collected demographic, health and dietary data on 1,101 individuals aged 18 through 65 with and without psychiatric disorders. Approximately 55 percent of the participants were female and 55 percent were Caucasian, with 36 percent identifying as African-American.

Those with psychiatric disorders were recruited from patients receiving care at the Sheppard Pratt Health System in Baltimore. Individuals with no history of psychiatric disorders were recruited from posted announcements at local health care facilities and universities in the region.

A study of their records between 2007 and 2017 showed that, unexpectedly, among people who had been hospitalized for mania, a history of eating cured meat before hospitalization were approximately 3.5 times higher than the group of people without a psychiatric disorder. Cured meats were not associated with a diagnosis of schizoaffective disorder, bipolar disorder in people not hospitalized for mania or in major depressive disorder. No other foods about which participants were queried had a significant association with any of the disorders, or with mania.

“We looked at a number of different dietary exposures and cured meat really stood out,” says Yolken. “It wasn’t just that people with mania have an abnormal diet.”

Nitrates have long been used as preservatives in cured meat products and have been previously linked to some cancers and neurodegenerative diseases, so Yolken suspected they may also explain the link to mood states such as mania.

The dietary survey did not ask about frequency or time frame of cured meat consumption, so the researchers couldn’t draw conclusions about exactly how much cured meat boosts one’s risk of mania, but Yolken hopes future studies will address this.

To get at the roots of the association, Yolken collaborated with researchers studying the impact of nitrates on rats.

Kellie Tamashiro, Ph.D., associate professor of psychiatry and behavioral sciences, and M.D./Ph.D. student Seva Khambadkone, both of Johns Hopkins, and others divided a group of otherwise healthy rats into two groups: one received normal rat chow, and the other received both normal chow and a piece of store-bought, nitrate-prepared beef jerky every other day. Within two weeks, the rats receiving the jerky showed irregular sleeping patterns and hyperactivity.

Next, the team worked with a Baltimore-based beef jerky company to create a special nitrate-free dried beef. They repeated the experiment, this time giving some rats the store-bought, nitrate-prepared jerky and others the nitrate-free formulation. The animals that ate the nitrate-free meat behaved similarly to a control group, while the animals that consumed the nitrates once again showed sleep disturbances and hyperactivity similar to that seen in patients with mania–increased activity during normal sleep times and in new environments.

The results were then replicated with a specially formulated rat chow that had either nitrate added directly to the chow, or no nitrate.

Importantly, the amount of nitrate being consumed on a daily basis by the rats¾when scaled up to the size of a human–was equivalent to the amount a person might eat for a daily snack, such as one beef jerky stick or hot dog.

“We tried to make sure the amount of nitrate used in the experiment was in the range of what people might reasonably be eating,” says Yolken.

When the group analyzed the gut bacteria of the different groups of rats, they found that animals with nitrate in their diet had different patterns of bacteria living in their intestines than the other rats. Moreover, the animals had differences in several molecular pathways in the brain that have been previously implicated in bipolar disorder.

While the team also cautions that it’s too early to take any clinical messages from the results, and occasional cured meat consumption is unlikely to spur a manic episode in most of the population, Yolken says the findings add to evidence of the multiple factors that contribute to mania and bipolar disorder.

“It’s clear that mania is a complex neuropsychiatric state, and that both genetic vulnerabilities and environmental factors are likely involved in the emergence and severity of bipolar disorder and associated manic episodes,” says Khambadkone. “Our results suggest that nitrated cured meat could be one environmental player in mediating mania.”

Yolken’s group recently published results of a separate study showing that when people with bipolar disorder are given probiotics–which can change the composition of gut bacteria–after a manic episode, they are less likely to be rehospitalized in the following six months. “There’s growing evidence that germs in the intestines can influence the brain,” says Yolken. “And this work on nitrates opens the door for future studies on how that may be happening.”

Public Release: 20-Jul-2018

Scientists reverse aging-associated skin wrinkles and hair loss in a mouse model

A gene mutation causes wrinkled skin and hair loss; turning off that mutation restores the mouse to normal appearance.

University of Alabama at Birmingham

BIRMINGHAM, Ala. – Wrinkled skin and hair loss are hallmarks of aging. What if they could be reversed?

Keshav Singh, Ph.D., and colleagues have done just that, in a mouse model developed at the University of Alabama at Birmingham. When a mutation leading to mitochondrial dysfunction is induced, the mouse develops wrinkled skin and extensive, visible hair loss in a matter of weeks. When the mitochondrial function is restored by turning off the gene responsible for mitochondrial dysfunction, the mouse returns to smooth skin and thick fur, indistinguishable from a healthy mouse of the same age.

“To our knowledge, this observation is unprecedented,” said Singh, a professor of genetics in the UAB School of Medicine.

Importantly, the mutation that does this is in a nuclear gene affecting mitochondrial function, the tiny organelles known as the powerhouses of the cells. Numerous mitochondria in cells produce 90 percent of the chemical energy cells need to survive.

In humans, a decline in mitochondrial function is seen during aging, and mitochondrial dysfunction can drive age-related diseases. A depletion of the DNA in mitochondria is also implicated in human mitochondrial diseases, cardiovascular disease, diabetes, age-associated neurological disorders and cancer.

“This mouse model,” Singh said, “should provide an unprecedented opportunity for the development of preventive and therapeutic drug development strategies to augment the mitochondrial functions for the treatment of aging-associated skin and hair pathology and other human diseases in which mitochondrial dysfunction plays a significant role.”

The mutation in the mouse model is induced when the antibiotic doxycycline is added to the food or drinking water. This causes depletion of mitochondrial DNA because the enzyme to replicate the DNA becomes inactive.

In four weeks, the mice showed gray hair, reduced hair density, hair loss, slowed movements and lethargy, changes that are reminiscent of natural aging. Wrinkled skin was seen four to eight weeks after induction of the mutation, and females had more severe skin wrinkles than males.

Dramatically, this hair loss and wrinkled skin could be reversed by turning off the mutation. The photos below show the hair loss and wrinkled skin after two months of doxycycline induction, and the same mouse a month later after doxycycline was stopped, allowing restoration of the depleted mitochondrial DNA.

Little change was seen in other organs when the mutation was induced, suggesting an important role for mitochondria in skin compared to other tissues.

The wrinkled skin showed changes similar to those seen in both intrinsic and extrinsic aging — intrinsic aging is the natural process of aging, and extrinsic aging is the effect of external factors that influence aging, such as skin wrinkles that develop from excess sun or long-term smoking.

Among the details, the skin of induced-mutation mice showed increased numbers of skin cells, abnormal thickening of the outer layer, dysfunctional hair follicles and increased inflammation that appeared to contribute to skin pathology. These are similar to extrinsic aging of the skin in humans. The mice with depleted mitochondrial DNA also showed changed expression of four aging-associated markers in cells, similar to intrinsic aging.

The skin also showed disruption in the balance between matrix metalloproteinase enzymes and their tissue-specific inhibitor — a balance of these two is necessary to maintain the collagen fibers in the skin that prevent wrinkling.

The mitochondria of induced-mutation mice had reduced mitochondrial DNA content, altered mitochondrial gene expression, and instability of the large complexes in mitochondria that are involved in oxidative phosphorylation.

Reversal of the mutation restored mitochondrial function, as well as the skin and hair pathology. This showed that mitochondria are reversible regulators of skin aging and loss of hair, an observation that Singh calls “surprising.”

“It suggests that epigenetic mechanisms underlying mitochondria-to-nucleus cross-talk must play an important role in the restoration of normal skin and hair phenotype,” Singh said, who has a secondary UAB appointment as professor of pathology. “Further experiments are required to determine whether phenotypic changes in other organs can also be reversed to wildtype level by restoration of mitrochondrial DNA.”

Public Release: 24-Jul-2018

New study: Omega-3s help keep kids out of trouble

Research led by UMass Lowell prof is one example of how diet, biology can prevent bad, even criminal behavior

University of Massachusetts Lowell

LOWELL, Mass. – Something as simple as a dietary supplement could reduce disruptive, even abusive behavior, according to newly released research by a team led by a UMass Lowell criminal justice professor.

Giving children omega-3 fatty acid supplements reduces disruptive behavior, which in turn had a positive effect on their parents, making them less likely to argue with each other and engage in other verbal abuse, according to Jill Portnoy, an assistant professor in UMass Lowell’s School of Criminology and Justice Studies.

“This is a promising line of research because omega-3 fatty acids are thought to improve brain health in children and adults. There is more to be learned about the benefits, but if we can improve people’s brain health and behavior in the process, that’s a really big plus,” said Portnoy, noting that a recent research review found that omega-3 supplements do not affect cardiovascular health.

The new research, published in the scholarly journal Aggressive Behavior, is just one example of how Portnoy is studying biological and social factors that can help explain and predict impulsive and risky behavior. The goal is to help determine effective ways to intervene before anti-social behavior escalates into crime.

That work takes Portnoy into the heart of the “nature versus nurture” debate – whether people who commit crimes have something in their physiological makeup that predisposes them to doing so or if social factors like abusive family situations lead them to it.

“Of course, it’s both,” she said, but exactly how is still to be determined. “Biology and social environment interact in complex ways that we’re just beginning to figure out. Before we can design effective interventions, we need to do research to understand what’s happening.”

Portnoy is exploring such a connection through another research project that is looking at how a low resting heart rate may lead to anti-social behavior.

“My theory is that a low resting heart rate might be an acquired, adaptive trait: If you are subjected to chronic or frequent stress as a child, you adapt by lowering your heart rate. The lower heart rate protects you by blunting your reaction to stressful events, but it can also lead to stimulation-seeking behavior. In other words, a stressful environment may cause physiological changes that lead to an increase in aggressive and impulsive behavior, in addition to causing the behavior directly,” she said.

Working with a counterpart at the University of Pennsylvania, where she earned her Ph.D. and taught before coming to UMass Lowell, Portnoy studied hundreds of youths in Pittsburgh, where she grew up. The researchers found that the youths with lower resting heart rates were more likely to act out as a form of sensation-seeking, including anti-social behavior, which can be especially problematic for individuals living where there are few options for positive forms of stimulation.

Portnoy, who now lives in Portsmouth, N.H., will continue her research on this topic this fall with the help of a dozen UMass Lowell undergrads who will intern with her on the Health, Stress and Behavior Study, researching the connection between stress, heart rate and behavior.

Through this study, Portnoy and her team will examine what she describes as a continuum of criminal behavior with the goal of finding new ways to prevent it.

“Many people break the law in small ways; for example, by driving a few miles over the speed limit. I’m interested in people who are behaving aggressively but not yet reaching the level of criminal behavior or maybe they’re committing more serious crimes like theft or assault, but haven’t been caught. They’re still exacting a toll on society. And if we want to design more general social interventions, like teaching people healthier ways to adapt to stress, then we shouldn’t just study those who get caught,” said Portnoy.

Public Release: 24-Jul-2018

Common painkillers triple harmful side effects in dementia

Commonly-prescribed opioid-based painkillers led to harmful side effects tripling in people with dementia

University of Exeter

Commonly-prescribed opioid-based painkillers led to harmful side effects tripling in people with dementia.

Researchers from the University of Exeter, King’s College London and the University of Bergen are presenting two studies at the Alzheimer’s Association International Conference 2018 (AAIC) highlighting a significant increase in harmful side effects related to the use of commonly prescribed opioid painkillers in people with dementia, compared to those on a placebo*. Researchers also identified a mechanism that may be causing the problem**.

In a randomized controlled trial of 162 Norwegian care home residents, the team found a significant rise in side effect such as personality changes, confusion and sedation, which can seriously impact people’s lives in dementia. The team is now calling for studies to examine appropriate dosing of painkillers such as buprenorphine for people with dementia.

Around half of people with dementia who are living in care homes experience clinically significant pain. Previous research has recognised that pain is often under-diagnosed and poorly managed in people with dementia, impacting on quality of life.

After paracetamol, opioid-based painkillers are often the next line of treatment for clinicians in people with dementia, and are prescribed to up to 40% of people with dementia living in care homes. They ease pain effectively, yet current prescribing guidance does not take into account the fact that people with dementia get effective pain relief from smaller doses than are commonly prescribed, and are particularly sensitive to adverse effects.

The trial team, led by the University of Bergen, studied 162 people from 47 Norwegian care homes who had advanced dementia and significant depression. In those who were assigned buprenorphine as part of their treatment pathway, harmful side-effects more than tripled. The researchers also found that those taking buprenorphine were significantly less active during the day.

Clive Ballard, Professor of Age-Related Diseases at the University of Exeter Medical School, said: “Pain is a symptom that can cause huge distress and it’s important that we can provide relief to people with dementia. Sadly at the moment we’re harming people when we’re trying to ease their pain. We urgently need more research in this area, and we must get this dosing right. We need to establish the best treatment pathway and examine appropriate dosing for people with dementia.”

Importantly, research led by Professor Ballard’s team and also presented at the conference gives insight into the mechanism of why people with dementia are more susceptible to opioid-based painkillers, suggesting they over-produce the body’s natural opioids.

The study treating arthritis in Alzheimer’s mice found increased sensitivity to the opioid-based painkiller morphine in mice with Alzheimer’s disease compared to those without. Those with Alzheimer’s disease responded to a much lower dose to ease pain, and experienced more adverse effects when the dose was increased to a normal level. Looking into this further the study found that the Alzheimer’s mice produced more of the body’s natural endogenous opioids such as endorphins. The study, presented as a poster at AAIC**, also concludes that dosing of opioid-based painkillers urgently needs to be reviewed in people with dementia to enable safe and effective treatment of pain, and prevent unnecessary harm and deaths.

Two posters relating to this work are presented at AAIC. They are:

*A Randomized, Placebo-Controlled Trial to Investigate Safety in People with Dementia or Buprenorphine Transdermal System for Pain Management. Authors are Ane Erdal; Elisabeth Flo; Dag Aarsland; Clive Ballard, and Bettina Sandgathe Husebø. Tuesday July 24.

**Impaired chronic pain-like behaviour and disruption of opioidergic system in TASTPM model of Alzheimer’s disease. Authors are Yahyah Aman, Thomas Pitcher, Clive Ballard, and Marzia Malcangio. Monday July 23.

Posters presented at conference have not yet been through the journal peer review process.

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Public Release: 30-Jul-2018

Depression linked to low blood levels of acetyl-L-carnitine

Stanford Medicine

People with depression have low blood levels of a substance called acetyl-L-carnitine, according to a Stanford University School of Medicine scientist and her collaborators in a multicenter study.

Naturally produced in the body, acetyl-L-carnitine is also widely available in drugstores, supermarkets and health food catalogs as a nutritional supplement. People with severe or treatment-resistant depression, or whose bouts of depression began earlier in life, have particularly low blood levels of the substance.

The findings, to be published online July 30 in the Proceedings of the National Academy of Sciences, build on extensive animal research. They mark the first rigorous indication that the link between acetyl-L-carnitine levels and depression may apply to people, too. And they point the way to a new class of antidepressants that could be freer of side effects and faster-acting than those in use today, and that may help patients for whom existing treatments don’t work or have stopped working.

Natalie Rasgon, MD, PhD, professor of psychiatry and behavioral sciences at Stanford, described the findings as “an exciting addition to our understanding of the mechanisms of depressive illness.”

“As a clinical psychiatrist, I have treated many people with this disorder in my practice,” she said.

Depression, also called major depressive disorder or clinical depression, is the most prevalent mood disorder in the United States and the world, affecting 8-10 percent of the general population at any given time, with every fourth person likely to experience the condition over the course of a lifetime.

“It’s the No. 1 reason for absenteeism at work, and one of the leading causes of suicide,” Rasgon said. “Worse, current pharmacological treatments are effective for only about 50 percent of the people for whom they’re prescribed. And they have numerous side effects, often decreasing long term compliance.”

Rasgon shares senior authorship of the study with Bruce McEwen, PhD, professor and chief of the Laboratory of Neuroendocrinology at The Rockefeller University in New York City. The lead author is Carla Nasca, PhD, a postdoctoral scholar in McEwen’s lab.

Results in animal studies

“In rodent experiments led by Dr. Nasca both here at Rockefeller and elsewhere previously, a deficiency of acetyl-L-carnitine was associated with depression-like behavior,” McEwen said. Oral or intravenous administration of acetyl-L-carnitine reversed the animals’ symptoms and restored their normal behavior, he said.

In those studies, the animals responded to acetyl-L-carnitine supplementation within a few days. Current antidepressants, in contrast, typically take two to four weeks to kick in — in animal experiments as well as among patients.

Nasca’s animal studies suggest that acetyl-L-carnitine, a crucial mediator of fat metabolism and energy production throughout the body, plays a special role in the brain, where it works at least in part by preventing the excessive firing of excitatory nerve cells in brain regions called the hippocampus and frontal cortex.

The new study, also initiated by Nasca, recruited 20- to 70-year-old men and women who had been diagnosed with depression and, amid episodes of acute depression, had been admitted to either Weill Cornell Medicine or Mount Sinai School of Medicine, both in New York City, for treatment. These participants were screened via a detailed questionnaire and assessed clinically, and their blood samples and medical histories were taken. Twenty-eight of them were judged to have moderate depression, and 43 had severe depression.

In comparing their blood samples with those of 45 demographically matched healthy people, the depressed patients’ acetyl-L-carnitine blood levels were found to be substantially lower. These findings held true for both men and women, regardless of age.

Lowest levels = worst symptoms

Further analysis showed that the lowest levels occurred among participants whose symptoms were most severe, whose medical histories indicated they were resistant to previous treatments, or whose onset of the disorder occurred early in life. Acetyl-L-carnitine levels were also lower among those patients reporting a childhood history of abuse, neglect, poverty or exposure to violence.

These patients, who collectively account for 25-30 percent of all people with major depression disorder, are precisely the ones most in need of effective pharmacological interventions, said Rasgon, who performed the bulk of the advanced data analysis for the study.

But she cautioned against rushing to the store to pick up a bottle of acetyl-L-carnitine and self-medicating for depression. “We have many previous examples of how nutritional supplements widely available over the counter and unregulated by the Food and Drug Administration — for example, omega-3 fatty acids or various herbal substances — are touted as panaceas for you-name-it, and then don’t pan out,” she said.

Big questions remain, she added. “We’ve identified an important new biomarker of major depression disorder. We didn’t test whether supplementing with that substance could actually improve patients’ symptoms. What’s the appropriate dose, frequency, duration? We need to answer many questions before proceeding with recommendations, yet. This is the first step toward developing that knowledge, which will require large-scale, carefully controlled clinical trials.”

Public Release: 1-Aug-2018

Active substance raises hopes of curing hepatitis E

Ruhr-University Bochum

An international team of researchers has now found a possible active substance against the virus in the naturally occurring substance silvestrol. The substance inhibited the replication of pathogens both in cell culture and in the mouse model. The researchers led by Dr Daniel Todt and Prof Dr Eike Steinmann from the Department of Medical and Molecular Virology at Ruhr-Universität Bochum (RUB) reported in the journal Antiviral Research on 23 July 2018.

Mahogany plants form active ingredient

Silvestrol is formed by around 400 different types of mahogany plants and can be extracted from their leaves. In the past, silvestrol was described as a potential active ingredient against certain tumours and Ebola, but has not yet been in clinical use.

When screening possible active substances against hepatitis E, the researchers – initially still at Twincore, Centre for Experimental and Clinical Infection Research in Hanover, then at the RUB – investigated the effect of silvestrol on the virus. “We first treated what are known as reporter viruses with silvestrol in cell cultures and found that they replicated less than without the treatment,” explains Daniel Todt.

RNA reveals the number of new viruses

In the next step, the researchers used stem cells that they had differentiated into liver cells. They infected them with hepatitis E viruses – both those they had previously produced in the laboratory and those that came from patients and had been purified. The researchers observed the course of infection with and without silvestrol for several days. “Using specific antibodies directed against the virus, we were able to measure how often the viruses replicated in the infected cells,” explains Daniel Todt.

The Result: Following treatment with silvestrol, the multiplication rate and the number of infected cells dropped sharply. “The effect of silvestrol was stronger than that of ribavirin, the only drug used to date to treat hepatitis E,” explains the researcher. This was shown in infections with all four known genetically different types of the virus that can make people ill.

In order to investigate whether the active substance also inhibits viral replication in living organisms, they tested its effect in mice that were implanted with human liver cells and infected with hepatitis E. Here, too, the treatment with silvestrol led to less replication of the viruses. There were no harmful side effects in small doses.

First port of call for hepatitis E research

These results raise hopes that silvestrol might be an effective treatment for hepatitis E. “The clinical potential must be explored in further studies,” says Eike Steinmann. “Our research is laying the foundations for this.”

The Bochum-based researchers are the first to have established a comprehensive test system for active substances against the hepatitis E virus, from cell culture and stem cells to animal models.

Hepatitis E

The hepatitis E virus (HEV) is the main cause of acute viral hepatitis. After the first documented epidemic outbreak from 1955 to 1956, more than 50 years passed before researchers intensively addressed the topic. Acute infections usually clear up by themselves in patients with an intact immune system. HEV can become chronic in patients with reduced or suppressed immune systems such as organ transplant recipients or HIV-infected patients. HEV is also particularly dangerous for pregnant women. Ribavirin is the only active substance currently in use, but it is not effective in all cases.

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Public Release: 3-Aug-2018

Low plasma levels of omega-3 fatty acids associated with preterm birth

Harvard T.H. Chan School of Public Health

Boston, MA – Pregnant women who had low plasma levels of long chain n-3 fatty acids in their first and second trimesters were at a significantly higher risk of early preterm birth when compared with women who had higher levels of these fatty acids, according to new research from Harvard T.H. Chan School of Public Health in collaboration with Statens Serum Institut in Copenhagen. The study suggests that low concentrations of certain long chain fatty acids–eicosapentaenoic acid and docosahexaenoic acid (EPA+DHA)–may be a strong risk factor for preterm birth.

“At a time when many pregnant women are hearing messages encouraging them to avoid intake of fish altogether due to mercury content, our results support the importance of ensuring adequate intake of long chain omega-3 fatty acids in pregnancy. Consumers should consult the guidance issued last year by the U.S. Food and Drug Administration and Environmental Protection Agency to make informed choices about the best types of fish to consume and avoid in pregnancy,” said lead author Sjurdur F. Olsen, adjunct professor of nutrition at Harvard Chan School and head of the Centre for Fetal Programming at Statens Serum Institut in Copenhagen, Denmark.

The study will be published online August 3, 2018, in EBioMedicine.

Preterm birth is a leading cause of neonatal death and is associated with cognitive deficiencies and cardiometabolic problems later in life among survivors. For decades, it has been hypothesized that high intake of EPA+DHA, which is found in cold-water fish such as Atlantic mackerel, anchovies, salmon, and tuna and also in leaner species such as cod and haddock, can reduce the risk of preterm birth. While some studies have supported this hypothesis, research findings have been inconsistent.

For this new study, researchers examined data from the Danish National Birth Cohort, a nationwide study that follows 96,000 children in Denmark through questionnaires and registry linkages. They analyzed blood samples from 376 women who gave birth very prematurely (prior to 34 weeks of gestation) between 1996 and 2003 and 348 women who had a full-term birth. All of the women gave blood samples during their first and second trimesters of pregnancy.

Analysis of the blood samples showed that women who were in the lowest quintile of EPA+DHA serum levels–with EPA+DHA levels of 1.6% or less of total plasma fatty acids–had a 10 times higher risk of early preterm birth when compared with women in the three highest quintiles, whose EPA+DHA levels were 1.8% or higher. Women in the second lowest quintile had a 2.7 times higher risk compared with women in the three highest quintiles.

The findings suggest that, among pregnant women with low levels of EPA+DHA, eating more fish or taking a fish oil supplement could potentially lower the risk of preterm birth. The authors cautioned, however, that broad generalizations about the study’s findings may be limited due to the fact that it was conducted in Demark, where preterm birth rates are low, and said the results should be replicated in other populations. They also cautioned that the findings may not solely reflect a variation in diet; variation in underlying genetic factors may also play a role.

“An effect of this magnitude is rare, but the precision of the estimate is tight, which supports the reliability these findings. It will be important to replicate these findings in other populations, but the results of this study certainly suggest that assessment of plasma EPA+DHA status in women has the potential to be used in the future to help predict women’s risk,” said co-author Jeremy Furtado, senior research scientist at Harvard Chan School.

“Early preterm birth has immense health, economic, and emotional costs. Our findings are consistent with the results of most randomized trials of long chain omega-3 fatty acid supplements in pregnancy and support the importance of ensuring adequate intake of these nutrients during pregnancy, either through fish intake or supplements, to help prevent early preterm birth,” said co-author Andrew Thorne-Lyman, an associate research scientist at Johns Hopkins Bloomberg School of Public Health who worked on this study while a faculty member at Harvard Chan School.

Public Release: 2-Aug-2018

Mushrooms of the Far East hold promise for the anti-cancer therapy

Mushrooms from the Far East area contain the natural chemical compounds, which could be used for the design of the novel drugs with highly specific anti-tumor activities and low-toxicity

Far Eastern Federal University

Mushrooms from the Far East area contain the natural chemical compounds, which could be used for the design of the novel drugs with highly specific anti-tumor activities and low-toxicity. These compounds may offer new avenues for oncology, providing us with either stand-alone alternatives to chemotherapy, chemopreventive medicines, or drugs to be used in combination with other therapies.

The international team of scientists from the Far Eastern Federal University (FEFU), University of Lausanne, and Federal Scientific Center of the East Asia Terrestrial Biodiversity FEB RAS describes the available body of research on four fungi species with high anti-cancer potential. The article is published in Oncotarget and contains the list of tumors, which were reported to be promising targets of the fungal compounds. Among them sarcoma, leukemia, rectum and colon cancer, stomach cancer, liver cancer, colon carcinoma and others.

For the purpose of the current study scientists chose mushrooms widely used in Asian and Far Eastern folk medicine: Fomitopsis pinicola, Hericium erinaceus, Inonotus obliquus, and Trametes versicolor. These species of fungi were shown to selectively target certain malignant tumors. The desired effect is achieved thanks to the various bioactive compounds contained in the mushrooms: polyphenols, polysaccharides, glucans, terpenoids, steroids, cerebrosides, and proteins. These substances are not only capable to hit different critical targets within cancer cells levels but also in certain cases to synergistically boost the chemo. Scientists emphasize that four species of fungi were chosen due to the fact that their medicinal properties are relatively well described. Some of them are already actively used for the anti-cancer drugs manufacturing in certain countires. Undoubtedly, there are many other species of fungi that contain chemical compounds to defeat cancer cells.

“In ancient China mushrooms were considered as the most effective treatment for the various types of tumors. Contemporary fungotherapy (treatment by means of mushrooms) represents a promising field for scientific research. The natural chemical compounds contained in fungi have a huge therapeutic and particularly the anti-cancer potential that has not been yet fully studied”, says Professor Vladimir Katanaev, Dr.Habil, Ph.D., Head of the Laboratory of Pharmacology of Natural Compounds of the Department of Pharmacology and Pharmacy of the School of Biomedicine, FEFU.

Another co-PI and corresponding author of this work, director of the center for genomic and regenerative medicine of the School of Biomedicine, FEFU, Alexander Kagansky, notes that despite that the interest in mushrooms studying has been growing exponentially over the past 60 years, about 90% of the fungal species have never been analyzed for their antibiotic and antitumor activities.

“Moreover, the significant part of cancer-related research of fungi deals merely with their toxicity to cancer cells, and the ability to stop the growth and development of cancer cells. The point is that such properties of the fungi compounds are equally detrimental to the healthy cells of the body”, comments on A. Kagansky. According to the scientist, it is necessary to research fungi for the chemical compounds capable of selective, targeted impact on cancer cells.

Vladimir Katanaev notes the importance of further research the immunomodulatory effect of fungi enriched with polysaccharides. According to him, immunomodulation can be attributed to indirect but effective methods of defeating cancer.

The first generation of natural medical compounds from mushrooms’ extracts wasn’t specific and has been applying widely for the therapy of all cancer types without consideration of tumor type properties. Such therapy damaged not only tumor cells but also healthy cells of the body. There were lots of heavy side-effects at times leading to the death of the patient due to the overdose.

Modern approaches to anti-cancer therapy are based on the targeted treatment with minimal or no consequences to the healthy cells and tissues. For this purpose, not only the general therapeutic properties of fungal chemical compounds are investigated but also the ways they differ in their action on different tumours.

The scientists hope that the high potential of the fungi for the anti-cancer therapy showcased in their article will encourage the further research at the junction of oncology and mycology. Currently in the laboratories of the School of Biomedicine (FEFU) led by Vladimir Katanaev and Alexander Kagansky,the new experiments are conducted to reveal the anti-cancer activities of the mushrooms extracts. This work is aimed at creating the new generation of highly specific low-toxic drugs, which could be specifically targeted on different tumor types.

Public Release: 7-Aug-2018

Soy diets might increase women’s bone strength

University of Missouri-Columbia

COLUMBIA, Mo. – Osteoporosis, decreased physical activity and weight gain are serious health concerns for postmenopausal women. Researchers from the University of Missouri now have discovered through a new animal study that soy protein found in food might counter the negative effects of menopause on bone and metabolic health. Moreover, the researchers believe that soy protein might also have positive impacts on bone strength for women who have not yet reached menopause.

“The findings suggest that all women might see improved bone strength by adding some soy-based whole foods, such as tofu and soy milk, to their diet,” said Pamela Hinton, professor of nutrition and exercise physiology. “We also believe that soy-based diets can improve metabolic function for postmenopausal women.”

Hinton and Victoria Vieira-Potter, co-author and associate professor of nutrition and exercise physiology, studied the effects of soy versus corn-based diets on rats selectively bred to have low fitness levels. Rats were again divided between those with and without ovaries to mimic effects of menopause. Prior research has found that these rats are good models for menopausal women. They compared the impact of the soy diet on bone strength and metabolic function to rats fed a corn-based, soy-free diet.

“Prior research has shown that these rats are good models, as average American women are relatively inactive both before, and especially after, menopause,” Vieira-Potter said. “As such, understanding how dietary protein sources, such as soy, can impact metabolism and bone health in these rats can help us better understand how such diets might impact women’s health across the lifespan.”

The researchers found that the tibia bones of the rats that were fed soy were stronger compared to the rats who were fed the corn-based diet, regardless of ovarian hormone status. Moreover, they found that the soy-based diet also improved metabolic function of the rats both with and without ovaries.

“Bottom line, this study showed that women might improve bone strength by adding some soy-based whole foods to their diet,” Hinton said. “Our findings suggest that women don’t even need to eat as much soy as is found in typical Asian diets, but adding some tofu or other soy, for example foods found in vegetarian diets, could help strengthen bones.”

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“Soy protein improves tibial whole-bone and tissue-level biomechanical properties in ovariectomized and ovary-intact, low-fit female rats,” recently was published in Bone Reports. Other MU researchers on the study included Laura Ortinau, Rebecca Dirkes, Emily Shaw, Matthew Richard and Terese Zidon. Steven Britton and Lauren Koch, both affiliated with the University of Michigan Medical School, also contributed to the study.

The study was funded by the National Center for Complementary and Integrated Health, the Office of Dietary Supplements and the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies.

The Department of Nutrition and Exercise Physiology is administered by the College of Agriculture, Food and Natural Resources, the College of Human Environmental Sciences and the School of Medicine.

Public Release: 14-Aug-2018

Chemicals found in vegetables prevent colon cancer in mice

The Francis Crick Institute

Chemicals produced by vegetables such as kale, cabbage and broccoli could help to maintain a healthy gut and prevent colon cancer, a new study from the Francis Crick Institute shows.

The research, published in Immunity, shows that mice fed on a diet rich in indole-3-carbinol – which is produced when we digest vegetables from the Brassica genus – were protected from gut inflammation and colon cancer.

While the health benefits of vegetables are well-established, many of the mechanisms behind them remain unknown. This study offers the first concrete evidence of how I3C in the diet can prevent colon inflammation and cancer, by activating a protein called the aryl hydrocarbon receptor (AhR).

Gut reactions

AhR acts as an environmental sensor, passing signals to immune cells and epithelial cells in the gut lining to protect us from inflammatory responses to the trillions of bacteria that live in the gut.

“We studied genetically modified mice that cannot produce or activate AhR in their guts, and found that they readily developed gut inflammation which progressed to colon cancer,” explains first author Dr Amina Metidji from the Francis Crick Institute. “However, when we fed them a diet enriched with I3C, they did not develop inflammation or cancer. Interestingly, when mice whose cancer was already developing were switched to the I3C-enriched diet, they ended up with significantly fewer tumours which were also more benign.”

By studying both mice and mouse gut organoids – ‘mini guts’ made from stem cells – the researchers found that AhR is vital for repairing damaged epithelial cells. Without AhR, intestinal stem cells fail to differentiate into specialised epithelial cells that absorb nutrients or generate protective mucus. Instead, they divide uncontrollably which can ultimately lead to colon cancer.

Preventing colon cancer

“Seeing the profound effect of diet on gut inflammation and colon cancer was very striking,” says senior author Dr Gitta Stockinger, Group Leader at the Francis Crick Institute. “We often think of colon cancer as a disease promoted by a Western diet rich in fat and poor in vegetable content, and our results suggest a mechanism behind this observation. Many vegetables produce chemicals that keep AhR stimulated in the gut. We found that AhR-promoting chemicals in the diet can correct defects caused by insufficient AhR stimulation. This can restore epithelial cell differentiation, offering resistance to intestinal infections and preventing colon cancer.

“These findings are a cause for optimism; while we can’t change the genetic factors that increase our risk of cancer, we can probably mitigate these risks by adopting an appropriate diet with plenty of vegetables.”

As well as correcting altered AhR dependent gene expression, dietary I3C also had a surprising effect on unmodified mice with normal AhR expression. While normal mice fed on standard or I3C-enriched food did not develop tumours during the study, those fed on a ‘purified control diet’ did.

An ‘optimal’ diet?

Laboratory mice are usually fed a standard grain-based ‘chow’ which contains a mix of ingredients and nutrients. For dietary studies, they are given a ‘purified control diet’ so that researchers know exactly what is in the food. These are designed to precisely fulfil the animal’s nutritional needs while being free of allergens, pathogens or variable ingredients found in standard chow.

Purified control diets contain exact mixtures of carbohydrates, proteins, fats and fibres enriched with vitamins and minerals. However, the latest study suggests that these diets have fewer AhR-promoting chemicals than the standard chow or the I3C-enriched diet.

“Normal mice on the purified control diet developed colon tumours within 10 weeks, whereas mice on the standard chow didn’t develop any,” explains co-corresponding author Dr Chris Schiering, who worked on the study at the Crick and now works at Imperial College London. “This suggests that even without genetic risk factors, a diet devoid of vegetable matter can lead to colon cancer.”

From mouse to man

To follow up on their surprising findings, the team are now hoping to do further experiments in organoids made from human gut biopsies and eventually human trials.

“A number of epidemiological studies suggested that vegetables may be protective against cancer,” explains Gitta. “However, there is very little literature on which vegetables are the most beneficial or why. Now that we’ve demonstrated the mechanistic basis for this in mice, we’re going to investigate these effects in human cells and people. In the meantime, there’s certainly no harm in eating more vegetables!”

Professor Tim Key, Cancer Research UK’s expert on diet and cancer, said: “This study in mice suggests that it’s not just the fibre contained in vegetables like broccoli and cabbage that help reduce the risk of bowel cancer, but also molecules found in these vegetables too. This adds to the evidence that a healthy diet, rich in vegetables, is important. Further studies will help find out whether the molecules in these vegetables have the same effect in people, but in the meantime there are already plenty of good reasons to eat more vegetables”

Public Release: 13-Aug-2018

Higher omega-3 index associated with better brain function in children

Wright On Marketing & Communications

New research published in the July edition of the Journal of Nutritional Biochemistry, has established a strong correlation between blood levels of omega-3s, especially docosahexaenoic acid (DHA), and better brain function in children two to six years old.

The objective of this cross-sectional study was to investigate the relationship between whole-blood fatty acids (FAs) and executive function in 307 children (two to six years old) from Northern Ghana. The aim of researchers was to examine the extent to which higher levels of EPA and/or DHA were associated with better cognitive performance. Dried blood spot samples were collected and analyzed for FA content.

The children underwent a battery of age-appropriate cognitive function tests. Specifically, the dimensional change card sort (DCCS) task was used to assess executive function.

The DCCS asks that the child sort a series of bivalent cards based on one of two instructed dimensions (i.e., either color or shape). Following sorting an initial series of eight cards based upon color, the child is instructed to switch the categorization dimension and sort another series of eight cards based upon shape. This dimensional change in sorting behavior provides an index of executive function as the child must suppress their previously learned set of rules (i.e., sorting by color) and attentional inertia towards those attributes in order to flexibly adjust their behavioral actions and attention to sort the cards by a new set of rules (i.e., sorting by shape).

The average Omega-3 Index (red blood cell EPA + DHA level) in this group was 4.6%, with a range of 2.3% to 11.7%. Significant differences in mean % total whole-blood fatty acids were observed between children who could not follow directions on the DCCS test (50% of the sample) and those who could (50% of the sample). Children with the highest levels of total omega-3s and DHA were three and four times, respectively, more likely to pass at least one condition of the DCCS test of executive function than those with the lowest levels.

This study has several strengths. First and foremost, it utilized an objective biomarker to assess dietary fatty acid intake (i.e., the Omega-3 Index), as opposed to other conventional and less precise methods such as food frequency questionnaires or diet history techniques. Food frequency questionnaires are not highly accurate at estimating circulating blood levels of fatty acids.

The authors concluded that these findings provided an “impetus for further studies into possible interventions to improve essential fatty acid status of children in developing countries.”

One of the study’s investigators, Dr. Bill Harris, founder of OmegaQuant, and co-inventor of the Omega-3 Index test, said the results are very encouraging for these children, who are probably the most disadvantaged when it comes to omega-3 consumption.

“Children in developing countries like Ghana do not have the access to omega-3-rich sources that children from other parts of the world do. This has several ramifications, particularly in the area of brain development and cognitive function. We were happy to see the positive correlation between omega-3 levels and better brain function, especially since an omega-3 deficiency is so easy to correct. All it requires is consuming more of the right omega-3s, especially DHA which in this case was the standout fatty acid here.”

Public Release: 21-Aug-2018

Clay to fight bacteria in wounds: An old practice may be a new solution

Mayo Clinic

ROCHESTER, Minn. – The use of mud or wet clay as a topical skin treatment or a poultice is a common practice in some cultures and the concept of using mud as medicine goes back to earliest times. Now Mayo Clinic researchers and their collaborators at Arizona State University have found that at least one type of clay may help fight disease-causing bacteria in wounds, including some treatment-resistant bacteria. The findings appear in the International Journal of Antimicrobial Agents.

“We showed that this reduced iron-bearing clay can kill some strains of bacteria under the laboratory conditions used, including bacteria grown as biofilms, which can be particularly challenging to treat,” says Robin Patel, M.D., a clinical microbiologist and infectious diseases specialist at Mayo Clinic and senior author of the study. Biofilms occur when bacteria attach to surfaces and develop a film or protective coating making them relatively resistant to antibiotics. They appear in two-thirds of the infections seen by physicians.

“This study is an important advance in understanding how clays, specifically blue clay from Oregon, have shown medicinal properties by attaching to pathogenic bacteria,” says Enriqueta Barrera, program director in the National Science Foundation’s Division of Earth Sciences, which funded the research.

In laboratory tests the researchers found the clay has antibacterial effects against bacteria such as Escherichia coli, and Staphylococcus aureus, including resistant strains such as CRE and MRSA. The clay suspension was effective against a number of bacteria both in their planktonic and biofilm states.

The research is preliminary and the authors caution that only one concentration of the clay suspension was tested, based on preliminary results. The lab tests are a first step in simulating the complex environment found in an actual infected wound. They also caution that not all types of clay are beneficial. Some may actually help bacteria grow. More research is needed to identify and reproduce the properties of clays that are antibacterial, with the goal of possibly synthesizing a consistent compound of the key minerals under quality control.

Public Release: 20-Aug-2018

Could vitamin B3 treat acute kidney injury?

Researchers discover mechanism that could lead to new, accessible treatment

Beth Israel Deaconess Medical Center

BOSTON – Acute kidney injury, an often fatal condition without a specific treatment, affects up to 10 percent of all hospitalized adults in the United States and 30-40 percent in low-income countries. The condition causes a build-up of waste products in the blood and an imbalance of fluids throughout the body. Acute kidney injury can occur from ailments that place the body into extreme stress – putting already hospitalized patients, particularly those in intensive care units, at risk.

A multidisciplinary research team led by Beth Israel Deaconess Medical Center nephrologist and principal investigator Samir M. Parikh, MD, has now determined that a form of vitamin B3 has the potential to prevent acute kidney injury. Published today in Nature Medicine, the findings bring clinicians one step closer to an accessible and safe therapy for patients who may be at risk.

Parikh and colleagues discovered that levels of nicotinamide adenine dinucleotide (NAD+) – the end result of vitamin B3 after it is ingested – declines in cases of acute kidney injury.

“We were able to detect a drop in NAD+ in the urine of high-risk patients who were either in an intensive care unit or undergoing a major surgery and found that oral vitamin B3 could safely elevate NAD+ in high-risk patients,” said Parikh, who is also an Associate Professor of Medicine at Harvard Medical School. “These findings are very early, but the results suggest that we could one day have a non-invasive test for NAD+ status and perhaps even treat acute kidney injury by boosting NAD+ levels.”

Parikh – along with first authors Mei Tran, a senior scientist in the Parikh laboratory, and Ali Poyan Mehr, MD, a nephrologist at BIDMC – made the discovery by studying the metabolic changes associated with acute kidney injury in a mouse model. A urine screen revealed high levels of quinolinate – a little-studied intermediate for making NAD+. This unusual pattern suggested a block at an enzyme called QPRT which is responsible for converting quinolinate to NAD+. With QPRT blocked, an explanation began to emerge for NAD+ depletion during acute kidney injury, which disrupts the body’s ability to manufacture NAD+.

The scientists tested that hypothesis by using CRISPR gene editing to create a mouse model with reduced QRPT but no kidney injury. The genetically altered rodents mimicked the pattern of acute kidney injury; decreased NAD+, increased urinary quinolinate and increased susceptibility to kidney injury. The experiments were the first to establish QRPT as a mediator of renal stress resistance.

In subsequent human studies, the team found high urinary quinolinate in patients undergoing major surgery at risk for acute kidney injury and confirmed this metabolite pattern in a separate study of 329 intensive care unit patients also at risk for acute kidney injury. The team then gave large doses of oral vitamin B3 to 41 cardiac surgery patients enrolled in a Phase 1 pilot study.

“Our results suggest that NAD+ biosynthesis becomes impaired during human acute kidney injury and that augmenting vitamin B3 levels may be safe and potentially beneficial to patients.” said Kamal Khabbaz, MD, Chief of Cardiac Surgery at the CardioVascular Institute at BIDMC, who co-led the clinical trial. “What’s more, we showed that urinary measurements in at-risk patients can indicate this impairment and, furthermore, predict adverse outcomes. Restoring NAD+ could constitute and important advance for patients at risk for acute kidney injury, though further studies are needed to verify these findings.”

Public Release: 20-Aug-2018

Consuming milk at breakfast lowers blood glucose throughout the day

Effects of protein composition and concentration detailed in a new study from the Journal of Dairy Science®

Philadelphia, August 20, 2018 – A change in breakfast routine may provide benefits for the management of type 2 diabetes, according to a new study published in the Journal of Dairy Science. H. Douglas Goff, PhD, and the team of scientists from the Human Nutraceutical Research Unit at the University of Guelph, in collaboration with the University of Toronto, examined the effects of consuming high-protein milk at breakfast on blood glucose levels and satiety after breakfast and after a second meal. Milk consumed with breakfast cereal reduced postprandial blood glucose concentration compared with water, and high dairy protein concentration reduced postprandial blood glucose concentration compared with normal dairy protein concentration. The high-protein treatment also reduced appetite after the second meal compared with the low-protein equivalent.

“Metabolic diseases are on the rise globally, with type 2 diabetes and obesity as leading concerns in human health,” Dr. Goff and team said. “Thus, there is impetus to develop dietary strategies for the risk reduction and management of obesity and diabetes to empower consumers to improve their personal health.”

In this randomized, controlled, double-blinded study, the team examined the effects of increasing protein concentration and increasing the proportion of whey protein in milk consumed with a high-carbohydrate breakfast cereal on blood glucose, feelings of satiety, and food consumption later in the day. Digestion of the whey and casein proteins naturally present in milk releases gastric hormones that slow digestion, increasing feelings of fullness. Digestion of whey proteins achieves this effect more quickly, whereas casein proteins provide a longer lasting effect.

Although the team only found a modest difference in food consumption at the lunch meal when increasing whey protein at breakfast, they did find that milk consumed with a high-carbohydrate breakfast reduced blood glucose even after lunch, and high-protein milk had a greater effect. Milk with an increased proportion of whey protein had a modest effect on pre-lunch blood glucose, achieving a greater decrease than that provided by regular milk.

According to Dr. Goff and colleagues, “This study confirms the importance of milk at breakfast time to aid in the slower digestion of carbohydrate and to help maintain lower blood sugar levels. Nutritionists have always stressed the importance of a healthy breakfast, and this study should encourage consumers to include milk.”

Public Release: 20-Aug-2018

Maple leaf extract could nip skin wrinkles in the bud

American Chemical Society

BOSTON, Aug. 20, 2018 — Maple trees are best known for their maple syrup and lovely fall foliage. But it turns out that the beauty of those leaves could be skin-deep — and that’s a good thing. Today, scientists report that an extract from the leaves may prevent wrinkles.

The researchers are presenting their results at the 256th National Meeting & Exposition of the American Chemical Society (ACS). ACS, the world’s largest scientific society, is holding the meeting here through Thursday. It features more than 10,000 presentations on a wide range of science topics.

The scientists had previously studied the chemistry and health benefits of sap and syrup obtained from sugar maple and red maple trees. Historical records suggested that other parts of the trees could also be useful, according to Navindra P. Seeram, Ph.D., the project’s principal investigator. “Native Americans used leaves from red maple trees in their traditional system of medicine,” he notes, “so why should we ignore the leaves?”

Skin elasticity is maintained by proteins such as elastin. Wrinkles form when the enzyme elastase breaks down elastin in the skin as part of the aging process. “We wanted to see whether leaf extracts from red maple trees could block the activity of elastase,” says Hang Ma, Ph.D., who is presenting the work at the meeting and is a research associate in Seeram’s lab.

The researchers, who are at the University of Rhode Island, zeroed in on phenolic compounds in the leaves known as glucitol-core-containing gallotannins (GCGs) and examined each compound’s ability to inhibit elastase activity in a test tube. The scientists also conducted computational studies to examine how the GCGs interact with elastase to block its activity, and how the molecules’ structures affect that blocking ability. GCGs containing multiple galloyl groups (a type of phenolic group) were more effective than those with a single galloyl group. But these compounds can do more than interfere with elastase. In prior work, Seeram’s group showed that these same GCGs might be able to protect skin from inflammation and lighten dark spots, such as unwanted freckles or age spots.

Seeram and Ma plan to do further testing. “You could imagine that these extracts might tighten up human skin like a plant-based Botox®, though they would be a topical application, not an injected toxin,” Seeram says. And the fact that the extracts are derived from trees would be appreciated by consumers who are looking for natural, plant-based ingredients in their skincare products.

The researchers have taken steps to get the extracts into products, having developed a proprietary patent-pending formulation containing GCGs from summer and fall maple leaves and maple sap, which they named MaplifaTM (pronounced “mape-LEAF-uh” to reflect its origin). They have licensed it to botanical extracts supplier Verdure Sciences based in Indiana and are hoping to eventually find a market for the formulation in the cosmetics sector or even in dietary supplements.

If these products come to fruition, the team’s findings could benefit the local economy. “Many botanical ingredients traditionally come from China, India and the Mediterranean, but the sugar maple and the red maple only grow in eastern North America,” Seeram says. Farmers in the region, who currently only harvest sap from the maple trees, could tap the leaves as a value-added product for an additional source of income. Even better, the process would be sustainable because leaves could be collected during normal pruning or when they fall from the trees in autumn.

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A press conference on this topic will be held Monday, August 20, at 1 p.m. Eastern time in the Boston Convention & Exhibition Center. Reporters may check-in at the press center, Room 102 A, or watch live on YouTube http://bit.ly/ACSLive_Boston2018. To ask questions online, sign in with a Google account.

The researchers acknowledge support and funding from the University of Rhode Island and Verdure Sciences.

The American Chemical Society, the world’s largest scientific society, is a not-for-profit organization chartered by the U.S. Congress. ACS is a global leader in providing access to chemistry-related information and research through its multiple databases, peer-reviewed journals and scientific conferences. ACS does not conduct research, but publishes and publicizes peer-reviewed scientific studies. Its main offices are in Washington, D.C., and Columbus, Ohio.

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Title

Inhibitory Effects of Glucitol-core Containing Gallotannins from a Proprietary Red Maple (Acer rubrum) Leaves Extract on Elastase Enzyme

Abstract

Skin wrinkling is a declining process of skin cell function associated with aging caused by the loss of skin elasticity over time. Skin elasticity is maintained by skin extracellular matrix proteins such as elastin. Elastase, a member of the chymotrypsin family of proteases, is responsible for the breakdown of skin elastin. Therefore, inhibition of elastase enzyme is a plausible management for skin elastin degradation and thus, elastase inhibitors, including natural products, are being investigated as anti-wrinkle cosmetic agents. We previously reported on the skin protective effects, including anti-glycation and anti-melanogenic properties, of a series of glucitol-core containing gallotannins (GCGs) from a proprietary phenolic-enriched red maple (Acer rubrum) leaves extract (MaplifaTM). However, the effect of these GCGs on elastase enzyme is unknown. Herein, we investigated the inhibitory effects of MaplifaTM GCGs including ginnalin B (GB), ginnalin C (GC), ginnalin A (GA), maplexin F (MF) and maplexin J (MJ) on elastase enzyme. The GCGs (at 500 μM) showed inhibitory activities ranging from 21.3 – 62.5% and the GCGs with multiple galloyl group including GA (2 galloyls), MF (3 galloyls), and MJ (4 galloyls) showed superior activity to those GCGs with a mono-galloyl group (namely, GB and GC). The mechanisms of the GCGs’ inhibitory effects on elastase enzyme were further studied by using an enzyme kinetic assay and computational docking method. Our data suggest that MaplifaTM GCGs may have anti-wrinkle activity through the inhibition of elastase enzyme warranting further studies on its cosmetic applications.

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