The Gary Null Show - 07.02.21

Sunflower peptide as 'template' for potential analgesic

Medical University of Vienna (Austria), June 28, 2021

A naturally occurring peptide in sunflower seeds was synthetically optimised and has now been identified as a potential drug for treating abdominal pain or inflammation (in the gastrointestinal tract, abdominal area and/or internal organs). That is the finding of an international study led by Christian Gruber from MedUni Vienna's Institute of Pharmacology (Center for Physiology and Pharmacology), which was conducted jointly with the University of Queensland and Flinders University in Australia and has now been published.

The scientific aim of the study is to find analgesics that are only active in the periphery and do not cross the blood-brain barrier, as an alternative to commonly used synthetic opioids. Gruber explains the background: "Morphine was one of the first plant-based medicines and was isolated from the dried latex of poppies more than 200 years ago. It binds to opioid receptors in the brain and is still regarded as the main pillar of pain therapy. However, there is a high risk of opioid addiction, and an overdose - as a result of this strong dependency - inhibits the breathing centre in the brain, which can result in respiratory depression and, in the worst case, in death." For this reason, researchers throughout the world are trying to make analgesics safer and to find active drug molecules that do not have the typical opioid side-effects. 

Sunflower extracts were to some extent used in traditional medicine for their anti-inflammatory and analgesic properties. In the current study, the scientists from Austria and Australia, primarily PhD student Edin Muratspahi?, isolated the plant molecule that may be responsible for this effect. Medicinal chemistry methods were then used to optimise the so-called sunflower trypsin inhibitor-1 (SFTI-1), one of the smallest naturally occurring cyclic peptides, by 'grafting' an endogenous opioid peptide into its scaffold. 

A total of 19 peptides were chemically synthesized based on the original SFTI-1 blueprint and pharmacologically tested. "One of these variants turned out to be our lead candidate for as potential innovative analgesic molecule, especially for pain in the gastrointestinal tract or in the peripheral organs. This peptide is extremely stable, highly potent and its action is restricted to the body's periphery. Its use is therefore expected to produce fewer of the typical side-effects associated with opioids," point out Gruber and Muratspahi?. 

The mode-of-action of the peptide is via the so-called kappa opioid receptor; this cellular protein is a drug target for pain relief, but is often associated with mood disorders and depression. The sunflower peptide does not act in the brain, hence there is much less risk of dependency or addiction. Furthermore, it selectively activates only the molecular signalling pathway that influences pain transmission but does not cause the typical opioid side-effects. The data of the animal model in the current study are very promising: the scientists see great potential for using this peptide in the future to develop a safe medication - which could be administered orally in tablet form - to treat pain in the gastrointestinal tract, and this drug could potentially also be used for related painful conditions, e.g. for inflammatory bowel disease. 

Using Nature's blueprint

The research of this MedUni Vienna laboratory led by Christian Gruber exploits the concept of using Nature's blueprint to develop optimised drugs. "We are searching through large databases containing genetic information of plants and animals, decoding new types of peptide molecules and studying their structure, with a view to testing them pharmacologically on enzymes or membrane receptors and ultimately utilizing them in the disease model," explains Gruber. Finally, potential drug candidates are chemically synthesised in a slightly modified form based on the natural blueprint, to obtain optimised pharmacological properties.

 

Study associates organic food intake in childhood with better cognitive development

Analysis of multiple prenatal and childhood environmental risk factors suggests that poor nutrition, house crowding and indoor air pollution are associated with poorer cognitive function

Barcelona Institute for Global Health (Spain), July 1, 2021

A study analysing the association between a wide variety of prenatal and childhood exposures and neuropsychological development in school-age children has found that organic food intake is associated with better scores on tests of fluid intelligence (ability to solve novel reasoning problems) and working memory (ability of the brain to retain new information while it is needed in the short term). The study, published in Environmental Pollution, was conceived and designed by researchers at the Barcelona Institute for Global Health (ISGlobal)--a centre supported by the "la Caixa" Foundation--and the Pere Virgili Health Research Institute (IISPV-CERCA). 

The explanation for this association may be that "healthy diets, including organic diets, are richer than fast food diets in nutrients necessary for the brain, such as fatty acids, vitamins and antioxidants, which together may enhance cognitive function in childhood," commented lead author Jordi Júlvez, a researcher at IISPV-CERCA who works closely with ISGlobal. 

The study also found that fast food intake, house crowding and environmental tobacco smoke during childhood were associated with lower fluid intelligence scores. In addition, exposure to fine particulate matter (PM2.5) indoors was associated with lower working memory scores. 

The study, titled "Early life multiple exposures and child cognitive function: A multi-centric birth cohort study in six European countries", used data on 1,298 children aged 6-11 years from six European country-specific birth cohorts (United Kingdom, France, Spain, Greece, Lithuania and Norway). The researchers looked at 87 environmental factors the children were exposed to in utero (air pollution, traffic, noise, various chemicals and lifestyle factors) and another 122 factors they were exposed to during childhood.

A Pioneering Study

The aim of the study was to analyse the influence of these exposures on the development and maturation of the human brain, since during childhood the brain is not yet fully developed for efficient defence against environmental chemicals and is particularly sensitive to toxicity, even at low levels that do not necessarily pose a risk to a healthy mature brain. 

The originality of the study lies in its use of an exposome approach, i.e. the fact that it takes into account the totality of exposures rather than focusing on a single one. This approach aims to achieve a better understanding of the complexity of multiple environmental exposures and their simultaneous effect on children's neurodevelopment. 

Another strength of the study, which analyses cohorts from six European countries, is its diversity, although this factor also poses the additional challenge of cultural differences, which can influence exposure levels and cognitive outcomes.

Notable Associations

The study found that the main determinants of fluid intelligence and working memory in children are organic diet, fast food diet, crowdedness of the family home, indoor air pollution and tobacco smoke. To date, there has been little research on the relationship between type of diet and cognitive function, but fast food intake has been associated with lower academic development success and some studies have also reported positive associations between organic diets and executive function scores. "In our study," explained Júlvez, "we found better scores in fluid intelligence and working memory with higher organic food intake and lower fast food intake." 

In contrast, exposure to tobacco smoke and indoor PM2.5 during childhood may negatively affect cognitive function by enhancing pro-inflammatory reactions in the brain. Still, according to Júlvez, it is worth bearing in mind that "the number of people living together in a home is often an indicator of the family's economic status, and that contexts of poverty favour less healthy lifestyles, which in turn may affect children's cognitive test scores". 

Some Surprising Findings 

The study also found some unexpected associations, which could be explained by confounding and reverse causality. For example, a positive association was found between childhood exposure to perfluorooctane sulfonic acid (PFOS) and cognitive function, even though PFOS is considered an endocrine disruptor that may alter thyroid function and negatively influence cognitive development. 

The study forms part of the large European project Human Early-Life Exposome (HELIX), as does another recent paper that used the same exposome and the same participants but looked at symptoms of attention deficit hyperactivity disorder (ADHD) and childhood behavioural problems. "We observed that several prenatal environmental pollutants (indoor air pollution and tobacco smoke) and lifestyle habits during childhood (diet, sleep and family social capital) were associated with behavioural problems in children," explained Martine Vrijheid, last author of the study and head of ISGlobal's Childhood and Environment programme.

"One of the strengths of this study on cognition and the earlier study on behavioural problems is that we systematically analysed a much wider range of exposure biomarkers in blood and urine to determine the internal levels in the model and that we analysed both prenatal and childhood exposure variables," concluded Vrijheid.

 

 

Extract of mulberry leaves partially restores the composition of intestinal microbiota and strengthens liver glycogen fragility in diabetic rats

Macau University of Science and Technology (China), June 28, 2021

According to news reporting out of Macau, People’s Republic of China, research stated, “Mulberry leaf as a traditional Chinese medicine is able to treat obesity, diabetes, and dyslipidemia. It is well known that diabetes leads to intestinal microbiota dysbiosis.”

Our news journalists obtained a quote from the research from the Macau University of Science and Technology, “It is also recently discovered that liver glycogen structure is impaired in diabetic animals. Since mulberry leaves are able to improve the diabetic conditions through reducing blood glucose level, it would be interesting to investigate whether they have any positive effects on intestinal microbiota and liver glycogen structure. In this study, we first determined the bioactive components of ethanol extract of mulberry leaves via high-performance liquid chromatography (HPLC) and liquid chromatography/mass spectrometry (LC/MS). Murine animal models were divided into three groups, normal Sprague-Dawley (SD) rats, high-fat diet (HFD) and streptozotocin (STZ) induced type 2 diabetic rats, and HFD/STZ-induced rats administered with ethanol extract of mulberry leaves (200 mg/kg/day). Composition of intestinal microbiota was analyzed via metagenomics by sequencing the V3-V4 region of 16S rDNAs. Liver glycogen structure was characterized through size exclusion chromatography (SEC). Both Student’s t-test and Tukey’s test were used for statistical analysis. A group of type 2 diabetic rat models were successfully established. Intestinal microbiota analysis showed that ethanol extract of mulberry leaves could partially change intestinal microbiota back to normal conditions. In addition, liver glycogen was restored from fragile state to stable state through administration of ethanol extract of mulberry leaves. This study confirms that the ethanol extract of mulberry leaves (MLE) ameliorates intestinal microbiota dysbiosis and strengthens liver glycogen fragility in diabetic rats.”

According to the news editors, the research concluded: “These finding can be helpful in discovering the novel therapeutic targets with the help of further investigations.”

 

 

Supplemental antioxidants may reduce exacerbations in cystic fibrosis

 

 

University of Colorado, July 2, 2021

An antioxidant-enriched vitamin may decrease respiratory exacerbations in people with cystic fibrosis(CF), according to new research published online iin the American Journal of Respiratory and Critical Care Medicine.

In "Effects of an Antioxidant-Enriched Multivitamin in Cystic Fibrosis: Randomized, Controlled, Multicenter Trial," Scott D. Sagel, MD, PhD, a professor of pediatrics at Children's Hospital Colorado and director of the University of Colorado Cystic Fibrosis Center, and coauthors report a 50 percent reduced risk of time to the first exacerbation requiring antibiotics in those receiving the supplemental antioxidants.

During the 16-week study of 73 patients (36 received supplemental antioxidants), 53 percent of the antioxidant-treated group experienced 28 exacerbations, compared to 68 percent of the control group who experienced 39 exacerbations.

The researchers also found that supplemental antioxidants increased circulating antioxidant concentrations of beta-carotene, coenzyme Q10, gamma-tocopherol (a form of vitamin E) and lutein and transiently decreased inflammation (at 4 weeks, but not 16 weeks) as measured by two blood-based biomarkers of inflammation, calprotectin and myeloperoxidase (MPO).

People with CF typically experience chronic bacterial infections, which lead to inflammation and the release of "vast amounts of reactive oxygen species in the airways," the authors wrote.

Normally, they added, the body would marshal an antioxidant defense to neutralize this oxidant stress, but CF is characterized by dietary antioxidant deficiencies. This contributes to an oxidant-antioxidant imbalance and more inflammation, which leads to lung damage and a progressive loss of lung function.

"Improving antioxidant status in CF is an important clinical goal and may have a positive effect on health," Dr. Sagel said. "Oral antioxidant formulations had been tested in CF with mixed results. However, there had not been a well-designed randomized controlled trial of an antioxidant 'cocktail' that included multiple antioxidants in a single formulation."

This phase 2 trial, conducted at 15 CF centers affiliated with the CF Foundation Therapeutics Development Network, enrolled patients who were 10 years and older (average age 22 years), with pancreatic insufficiency, which causes malabsorption of antioxidants. Participants had an FEV1, the measure of how much air can be forcefully exhaled in one second, between 40 and 100 percent of what would be predicted, based on age, gender, height and a range of other characteristics.

Patients in the control group received a multivitamin without antioxidant enrichment. The two groups tolerated their vitamins equally well, and there were no differences in adverse events between the two groups.

The study did not meet its primary endpoint: change in sputum MPO concentration over 16 weeks. The authors chose sputum MPO "rather than another marker of airway inflammation such as neutrophil elastase because MPO generates reactive oxidant species as part of its function in innate host defense mechanisms, and is considered by many a marker of oxidative stress."

"While the antioxidant supplement did not appear to exert sustained anti-inflammatory effects, we believe its effect on time to first pulmonary exacerbation was significant and clinically meaningful," Dr. Sagel said, adding that the improvement in antioxidant status alone may justify its use. "Developing safe and effective anti-inflammatory treatments remains a key priority of the CF community."

 

Maternal diets rich in Omega-3 fatty acids may protect offspring from breast cancer

Marshall University School of Medicine, June 28, 2021

According to researchers at Marshall University, a maternal diet rich in Omega-3 fatty acids protects from breast cancer development in offspring. In a new studyrecently published by Frontiers in Cell and Developmental Biology, researchers noted a significant difference in mice from mothers that were fed a diet rich in canola oil, compared with mothers fed a diet rich in corn oil. A maternal Omega 3-rich diet affected genome-wide epigenetic landscape changes in offspring and potentially modulated gene expression patterns.

Dr. Ata Abbas, a former postdoctoral research fellow in Marshall's Department of Biological Sciences, headed a research team under the leadership of Dr. Philippe Georgel in the College of Science. Research was done in the Cell Differentiation and Development Center at Marshall as part of a collaborative effort with the Joan C. Edwards School of Medicine's Department of Biochemistry and Microbiology, under the leadership of Dr. W. Elaine Hardman.

Researchers noticed a three-week delay in mortality in mice whose mothers were fed canola oil versus corn oil. The early delay in mortality was significantly different, but the ultimate overall survival rate was not. Eventually, all the mice developed tumors, but the ones fed canola oil had tumors that were slower-growing and smaller than the mice fed corn oil. Translated to human time scale, the duration of the protective effect linked to the maternal diet would be equivalent to several months (Sengupta et al., 2016).

This study is among a body of work done by Marshall University scientists and others looking at the link between Omega-3 fatty acids and reduced incidence of various types of cancer including, but not restricted to, Chronic Lymphocytic Leukemia and Diffuse Large B-Cell Lymphoma.

"The issue of parental diet and inter-generational transmission has become an important field of research; however, the mode of action often remains partially elusive," said Georgel, a professor in the Department of Biological Sciences at Marshall. "The MU research group focused on 'epigenetic' aspects of trans-generational transmission to explain the reported role of Omega-3 fatty acids. Epigenetics involves changes in gene expression which are not linked to changes in genetic sequences. These results have the potential to promote the design of simple changes in diet which would allow for reduced onset of various types of cancer, not only for the individuals using that diet but also for their offspring."

 

 

Compounds found in green tea and wine may block formation of toxic metabolites

Tel Aviv University (Israel), July 2, 2021

A new Tel Aviv University study suggests there is hope of treating certain inborn congenital metabolic diseases -- a hope found in green tea and in red wine.

Most people with inherited metabolic disorders are born with a defective gene that results in a critical enzyme deficiency. In the absence of a cure, many patients with inborn congenital metabolic disorders must adhere to a strict and demanding diet their entire lives. This new research finds that certain compounds found naturally in green tea and red wine may block the formation of toxic metabolites.

The research was led by Prof. Ehud Gazit of TAU's Faculty of Life Sciences and his doctoral student Shira Shaham-Niv. It was published in the Nature group journal Communications Chemistry.

The researchers considered two compounds: (1) epigallocatechin gallate, known as EGCG, found naturally in green tea, which has attracted attention within the medical community for its potential health benefits; and (2) tannic acid, found in red wine, which is known to prevent the formation of toxic amyloid structures that cause neurodegenerative disorders such as Alzheimer's and Parkinson's disease.

"In the case of inborn congenital metabolic diseases, the body does not produce a vital metabolic enzyme," Shaham-Niv said. "As a result, metabolites -- substances that are, among other things, the building blocks of DNA and proteins -- accumulate in the body. Such uncontrolled accumulation is toxic and can cause severe developmental and mental disorders.

"Our new study demonstrates once again the ability of nature to produce the best candidate of drugs to treat some of the worst human maladies."

Collectively, this group of disorders constitutes a significant portion of pediatric genetic diseases. The disease phenylketonuria (PKU), which produces the aggregation of the metabolite phenylalanine, is one common inborn metabolic disease. Infants with PKU must adhere to a strict diet free of phenylalanine for the rest of their lives. If they don't, they may face severe debilitating developmental problems.

"But this is an incredibly difficult task, since phenylalanine is found in most of the food products that we consume," Shaham-Niv said. "The avoidance of certain substances is the only way to prevent the debilitating long-term effects of inborn congenital metabolic disorders. We hope that our new approach will facilitate the development of new drugs to treat these disorders."

The new research is based on two previous studies conducted at Prof. Gazit's TAU laboratory. In the first study, phenylalanine was shown to be capable of self-assembly and of forming amyloid structures like those seen in Alzheimer's, Parkinson's and other neurodegenerative diseases. In the second study, by Shaham-Niv, other metabolites that accumulate in other inborn congenital metabolic diseases were also shown to undergo self-assembly processes and form toxic amyloid aggregates.

"Both studies led to an overhaul in the research community's understanding of metabolic diseases," Shaham-Niv said. "In our new study, we examined whether the molecules identified in past studies on Alzheimer's disease and other amyloid diseases, which are known to inhibit the formation of amyloid aggregates, could also help counteract the amyloid formation process of metabolites in metabolic diseases."

The new research focused on EGCG and tannic acid using test tubes and culture cell systems. The two substances were tested on three metabolites related to three innate metabolic diseases: adenine, cumulative tyrosine and phenylalanine. The results were promising. Both tannic acid and EGCG were effective in blocking the formation of toxic amyloid structures. The researchers also used computer simulations to verify the mechanism driving the compounds.

"We are entering a new era of understanding the role and the importance of metabolites in various diseases, including metabolic diseases, neurodegenerative diseases and even cancer," Shaham-Niv concluded. "The tools we have developed are ground-breaking and have tremendous potential to help a wide range of patients in the future."

 

 

 

People with fibromyalgia are substituting CBD for opioids to manage pain

University of Michigan, June 24, 2021

Fibromyalgia is one of many chronic pain conditions that remains stubbornly difficult to treat. 

As the ravages of the opioid epidemic lead many to avoid these powerful painkillers, a significant number of people with fibromyalgia are finding an effective replacement in CBD-containing products, finds a new Michigan Medicine study. 

CBD, short for cannabidiol, is the second most common cannabinoid in the cannabis plant, and has been marketed for everything from mood stabilization to pain relief, without the intoxicating effects produced by the most common cannabinoid, THC. THC, which stands for delta-9-tetrahydrocannabinol, is the ingredient in marijuana that causes people to feel high.

The cannabis industry has exploded, aided by the legalization of medical and recreational marijuana in states around the United States and the removal of hemp-derived CBD from Schedule 1 status--reserved for drugs with no currently accepted medical use and a high potential for abuse--at the federal level. 

Previous research shows that some people substitute medical cannabis (often with high concentrations of THC) for opioids and other pain medications, reporting that cannabis provides better pain relief and fewer side effects. However, there is far less data on CBD use.

"CBD is less harmful than THC, as it is non-intoxicating and has less potential for abuse," said Kevin Boehnke, Ph.D., a research investigator in the Department of Anesthesiology and the Chronic Pain and Fatigue Research Center. "If people can find the same relief without THC's side effects, CBD may represent a useful as a harm reduction strategy."

Boehnke and his team surveyed people with fibromyalgia about their use of CBD for treatment of chronic pain. 

"Fibromyalgia is not easy to treat, often involving several medications with significant side effects and modest benefits," Boehnke explained. "Further, many alternative therapies, like acupuncture and massage, are not covered by insurance."

For this study, the team focused on 878 people with fibromyalgia who said they used CBD to get more insight into how they used CBD products. 

The U-M team found that more than 70% of people with fibromyalgia who used CBD substituted CBD for opioids or other pain medications. Of these participants, many reported that they either decreased use or stopped taking opioids and other pain medications as a result. 

"I was not expecting that level of substitution," said Boehnke, noting that the rate is quite similar to the substitution rate reported in the medical cannabis literature. People who said they used CBD products that also contained THC had higher odds of substitution and reported greater symptom relief.

Yet the finding that products containing only CBD also provided pain relief and were substituted for pain medications is promising and merits future study, noted Boehnke. 

The team noted that much of the widespread use of CBD is occurring without physician guidance and in the absence of relevant clinical trials. "Even with that lack of evidence, people are using CBD, substituting it for medication and doing so saying it's less harmful and more effective," he said. 

Boehnke stressed the need for more controlled research into how CBD may provide these benefits, as well as whether these benefits may be due to the placebo effect. 

Clinically, opening up lines of discussion around CBD use for chronic pain is imperative, said Boehnke, for medication safety reasons as well as for "enhancing the therapeutic alliance and improving patient care."