University of Copenhagen (Denmark), August 3, 2021
While it is widely known that regular physical exercise decreases the risk of virtually all chronic illnesses, the mechanisms at play are not fully known. Now scientists at the University of Copenhagen have discovered that the beneficial effects of physical exercise may in part result from changes to the structure of our DNA. These changes are referred as “epigenetic.”
DNA is the molecular instruction manual found in all our cells. Some sections of our DNA are genes, which are instructions for building proteins—the body’s building blocks—while other sections called enhancers regulate which genes are switched on or off, when, and in which tissue. The scientists found, for the first time, that exercise rewires the enhancers in regions of our DNA that are known to be associated with the risk to develop disease.
“Our findings provide a mechanism for the known beneficial effects of exercise. By connecting each enhancer with a gene, we further provide a list of direct targets that could mediate this effect,” says Professor Romain Barrès from the Novo Nordisk Foundation Center for Basic Metabolic Research, the senior author of the research, which was published in Molecular Metabolism.
Exercise improves health of organs including the brain
The team of scientists hypothesized that endurance exercise training remodels the activity of gene enhancers in skeletal muscle. They recruited healthy young men and put them through a six-week endurance exercise program. The scientists collected a biopsy of their thigh muscle before and after the exercise intervention and examined if changes in the epigenetic signature of their DNA occurred after training.
The scientists discovered that after completing the endurance training program, the structure of many enhancers in the skeletal muscle of the young men had been altered. By connecting the enhancers to genetic databases, they discovered that many of the regulated enhancers have already been identified as hotspots of genetic variation between individuals—hotspots that have been associated with human disease.
The scientists speculate that the beneficial effects of exercise on organs distant from muscle, like the brain, may largely be mediated by regulating the secretion of muscle factors. In particular, they found that exercise remodels enhancer activity in skeletal muscle that are linked to cognitive abilities, which opens for the identification of exercise training-induced secreted muscle factors targeting the brain.
“Our data provides evidence of a functional link between epigenetic rewiring of enhancers to control their activity after exercise training and the modulation of disease risk in humans,” says Assistant Professor Kristine Williams, the lead author of this study.
According to news originating from Lanzhou, People’s Republic of China, research stated, “There are few effective medications to treat Alzheimer’s disease (AD). It has been suggested that several ginsenosides possess mild or moderate anti-AD activity.”
Our news journalists obtained a quote from the research from Lanzhou University, “In our present work, a preferred combined ginsenosides was shown to have a more significant benefit effect on AD-like symptoms of worm paralysis and hypersensitivity to exogenous 5-HT in. The combined ginsenosides can suppress Ab deposits and Ab oligomers, alleviating the toxicity induced by Ab overexpression more effectively than used alone. Its anti-AD effect was partially abolished by RNAi knocked down or inactivation by point mutation, but not by or RNAi knocked down. Furthermore, it markedly activated gene expression downstream of HSF-1. Our results demonstrated that HSF-1 signaling pathway exerts an important role in mediating the therapeutic effect of combined ginsenosides on AD worms.”
According to the news editors, the research concluded: “These results provided powerful evidences and theoretical foundation for reshaping medicinal products of ginsenosides and ginseng on prevention of neurodegenerative diseases.”
This research has been peer-reviewed.
Limonene may be useful to prevent neuronal effects induced by amyloid beta
University of Naples (Italy), July 28, 2021
According to news reporting out of Naples, Italy, research stated, “Many natural-derived compounds, including the essential oils from plants, are investigated to find new potential protective agents in several neurodegenerative disorders such as Alzheimer’s disease (AD). In the present study, we tested the neuroprotective effect of limonene, one of the main components of the genus Citrus, against the neurotoxicity elicited by A beta(1-42) oligomers, currently considered a triggering factor in AD.”
Our news journalists obtained a quote from the research from the University of Naples Federico II, “To this aim, we assessed the acetylcholinesterase activity by Ellman’s colorimetric method, the mitochondrial dehydrogenase activity by MTT assay, the nuclear morphology by Hoechst 33258, the generation of reactive oxygen species (ROS) by DCFH-DA fluorescent dye, and the electrophysiological activity of K(V)3.4 potassium channel subunits by patch-clamp electrophysiology. Interestingly, the monoterpene limonene showed a specific activity against acetylcholinesterase with an IC50 almost comparable to that of galantamine, used as positive control. Moreover, at the concentration of 10 mu g/mL, limonene counteracted the increase of ROS production triggered by A beta(1-42) oligomers, thus preventing the upregulation of K(V)3.4 activity. This, in turn, prevented cell death in primary cortical neurons, showing an interesting neuroprotective profile against A beta(1-42)-induced toxicity.”
According to the news editors, the research concluded: “Collectively, the present results showed that the antioxidant properties of the main component of the genus Citrus, limonene, may be useful to prevent neuronal suffering induced by A beta(1-42) oligomers preventing the hyperactivity of K(V)3.4.”
Effect of six months pranayama training on stress-induced salivary cortisol response among adolescents – Randomised controlled study
Sri Ramachandra Medical College and Research Institute (India), August 1, 2021
A combination of yoga practices has been documented to reduce stress and stress-induced cortisol levels. The objective of the current study is to examine the effects of six months of a single pranayama practice (Bhramari [Bhr. P]) on reducing salivary cortisol response to the cold pressor test (CPT) among adolescents.
Methods
Twenty-six healthy adolescents between the ages of 11 and 19 were randomly assigned to either yoga group (n-13) or control group (n-13). Yoga group participants were trained to do Bhr. P for 45 minutes, thrice a week for six months. All participants underwent CPT at baseline and at end of six months. Saliva samples were collected at baseline (t0), at 20 min (t1), 40 min (t2), and 60 min after the CPT (t3).
Results
Contradictory to our hypothesis, participants in the yoga group exhibited a higher salivary cortisol response to the CPT at t1 (p = 0.04) when compared to the control group. However, the t3 salivary cortisol levels showed a statistically significant reduction (p = 0.03) in yoga group when compared to the control group. A significant interaction with time (F (1, 88) = 316.5, p = .001, ηp2:0.91)andbetween the group × time (F (3, 88) = 2.83, p = 0.04, ηp2:0.8)was found after the intervention.
Conclusions
An increase in the cortisol responsiveness observed in the study is an indication of the adaptive capability achieved through regular yoga training, evidenced by an initial rise in cortisol followed by a rapid fall below baseline after 60 minutes. Further research is required to conclusively determine the changes in cortisol levels over time in response to stress in long-term yoga practitioners.
Melatonin inhibits triple-negative breast cancer progression
Sun Yat-sen University Cancer Center (China), August 2, 2021
According to news reporting from Sun Yat-sen University Cancer Centerby NewsRx journalists, research stated, “Melatonin has been reported to have tumor-suppressive effects via comprehensive molecular mechanisms, and long non-coding RNAs (lncRNAs) may participate in this process.”
The news journalists obtained a quote from the research from Sun Yat-sen University Cancer Center: “However, the mechanism by which melatonin affects the function of lncRNAs in triple-negative breast cancer (TNBC), the most aggressive subtype of breast cancer, is still unknown. Therefore, we aimed to investigate the differentially expressed mRNAs and lncRNAs in melatonin-treated TNBC cells and the interaction mechanisms. Microarray analyses were performed to identify differentially expressed mRNAs and lncRNAs in TNBC cell lines after melatonin treatment. To explore the functions and underlying mechanisms of the mRNAs and lncRNAs candidates, a series of in vitro experiments were conducted, including CCK-8, Transwell, colony formation, luciferase reporter gene, and RNA immunoprecipitation (RIP) assays, and mouse xenograft models were established. We found that after melatonin treatment, FUNDC1 and lnc049808 downregulated in TNBC cell lines. Knockdown of FUNDC1 and lnc049808 inhibited TNBC cell proliferation, invasion, and metastasis.”
According to the news reporters, the research concluded: “Moreover, lnc049808 and FUNDC1 acted as competing endogenous RNAs (ceRNAs) for binding to miR-101. These findings indicated that melatonin inhibited TNBC progression through the lnc049808-FUNDC1 pathway and melatonin could be used as a potential therapeutic agent for TNBC.”
Your soap and toothpaste could be messing with your microbiome
University of Chicago, August 1, 2021
Antimicrobial chemicals found in common household products could be wreaking havoc with people’s guts, according to a research paper out this week in the journal Science.
Triclosan is an antibacterial compound used in soaps, detergent and toothpaste, as well as toys and plastics. It was originally only used in hospitals, but it found its way into homes as Americans became more germ-phobic. (However, recent studies have found it no more effective at killing bacteria than plain soap. )
The latest research paper, written by academics from the University of Chicago, focused on the lesser-known effects of triclosan exposure on the bacteria in people’s guts.
Disturbing the human microbiome has been “linked to a wide array of diseases and metabolic disorders, including obesity, inflammatory bowel disease (IBD), irritable bowel syndrome (IBS) and behavioral and metabolic disorders,” wrote the paper’s authors, Alyson L Yee and Jack A Gilbert.
Yee and Gilbert examined conflicting research on just how the chemical impacts gut microbiomes. Studies using zebrafish and fathead minnows found that triclosan changed gut bacteria, but that the microbiomes recovered once exposure to the chemical was stopped. However, another study on biofilms in rivers found that the gut remained altered even after triclosan was removed.
To test the chemical’s effect in humans, researchers from Stanford and Cornell universities gave seven volunteers triclosan-containing products, such as toothpaste and liquid soap, to use for four months. After that period, the same volunteers were switched to products without triclosan. The volunteers were compared with a second group who first used the non-triclosan products, then changed to those containing triclosan.
The results showed that more triclosan was found in the urine of all the participants during the periods when they were using triclosan-containing products.
Yee and Gilbert also suggested that exposure to triclosan could be even more detrimental to the health of developing fetuses and newborns than to adults. A 2014 New York University study found that gut disruptions in early infancy could have lasting negative effects on immune and brain development.
The authors suggest that further studies are needed to understand the chemical’s effects on the human body.
Triclosan could also be contributing to antibiotic resistance, which scientists believe is caused by the overuse of antimicrobials in humans and animals. There are partial bans of the chemical in the European Union and in Minnesota, and the FDA says it will continue reviewing the chemical for its safety.
“Future research should explore the role of dose, timing, and route of triclosan exposure,” the paper’s authors wrote. “Humans are exposed to triclosan transiently and in small doses, but the presence of triclosan in surface, ground and drinking water indicates its potential to persist and accumulate in the environment.”
Chemical in essential oils may treat Parkinson’s disease
Sungkyunkwan University School of Medicine (South Korea) and Johns Hopkins University, August 3, 2021
In Parkinson’s, dopamine-producing neurons (nerves) in a part of the brain called the substantia nigra progressively die off.
Dopamine neurons are essential for movement and cognition, so their gradual loss over several years causes worsening symptoms, such as tremors, muscle rigidity, difficulty walking, and dementia.
There are currently no proven therapies to delay or prevent the progression of Parkinson’s.
Drugs such as L-DOPA boost dopamine levels in the brain and improve dopamine nerve signaling, which helps alleviate motor symptoms. These treatments do not slow the progressive loss of dopamine nerves, however.
So the discovery by researchers of a compound that prevents the death of dopamine neurons in a mouse model of Parkinson’s disease could herald a step change in treatment.
The compound, called farnesol, occurs naturally in plants and is a component of several essential oils, including citronella, lemongrass, and balsam. It has long featured as an ingredient in the manufacture of perfumes. The compound is also widespread in animal tissues.
“Parkinson’s is what happens when dopamine-producing cells in the brain die, so this study is important as it highlights a new pathway that could target and protect these brain cells in a person with Parkinson’s,” said Prof. David Dexter, Ph.D., associate director of research at the charity Parkinson’s UK, who was not involved in the study.
Nearly 1 million people in the United States and more than 10 million worldwide are living with Parkinson’s disease. It is the fastest growing neurological conditions in the world.
“[T]he need for a new treatment [that] could slow or stop Parkinson’s in its tracks has never been more urgent,” Prof. Dexter told Medical News Today.
“Designing more potent drugs replicating the action of this natural compound — farnesol — would be the next steps for researchers to progress this into clinical trials and potentially hold the key for a groundbreaking new treatment,” he said.
The new research, led by scientists at Sungkyunkwan University School of Medicine in Suwon, South Korea, and Johns Hopkins University School of Medicine in Baltimore, MD, appears in Science Translational Medicine.
Destination PARIS
The researchers began by screening a large library of drugs to find a compound that inhibits a protein called PARIS, which is implicated in the death of dopamine neurons in Parkinson’s.
PARIS slows down the manufacture of another protein, PGC-1 alpha, which shields brain cells from highly reactive oxygen molecules.
If levels of PGC-1 alpha are low, the reactive molecules eventually kill the cells.
The screening process identified farnesol as a potent inhibitor of PARIS. Importantly, people can take the drug orally, and it can cross the blood-brain barrier to protect brain cells.
Farnesol chemically alters PARIS in a process known as farnesylation. The researchers were intrigued to discover from postmortem studies that levels of farnesylated PARIS were lower in the substantia nigra of people with Parkison’s compared with controls.
This finding suggests that reduced farnesylation of PARIS contributes to the death of dopamine neurons in Parkinson’s.
To investigate whether farnesol can protect neurons, the researchers fed mice either a regular diet supplemented with farnesol or the regular diet alone for 1 week.
They then injected fibrils of a misfolded protein called alpha-synuclein — a hallmark of Parkinson’s — into the animals’ brains.
The mice that had eaten the farnesol-supplemented diet went on to perform twice as well on standard tests of strength and coordination compared with the mice that ate an ordinary diet.
The researchers subsequently discovered that the mice on the farnesol diet had twice as many healthy dopamine neurons in their brains.
The brains of the mice that ate a normal diet contained about 55% less of the protective protein PGC-1 alpha than those of the mice with the farnesol-supplemented diet.
Blocking a molecular switch
In test-tube experiments, the scientists found that when farnesol binds to PARIS, it changes the other protein’s shape. This prevents PARIS from interfering with the production of PGC-1 alpha.
“[T]his is kind of like putting a cover over a light switch to keep PARIS from turning off the cellular switch controlling production of PGC-1 alpha,” explained James C. Beck, Ph.D., chief scientific officer at the Parkinson’s Foundation, who was not involved in the study.
He said that scientists have recognized PGC-1 alpha for some time as a potential target for new Parkinson’s disease drugs because high levels can protect dopamine neurons.
“There are several ways to activate PGC-1 alpha, but farnesol is definitely unique,” he told MNT.
Although other drugs under development stimulate PGC-1 alpha directly, he said, this will not help if levels of the protective protein are too low.
In contrast, farnesol works by boosting the production of PGC-1 alpha, ensuring that enough is available to prevent dopamine neurons from dying.
The scientists behind the new research are planning a clinical trial of farnesol in patients with Parkinson’s disease.
“Issues such as formulation and dose need to be worked out,” said co-senior author Ted Dawson, M.D., Ph.D., director of the Johns Hopkins Institute for Cell Engineering and professor of neurology at Johns Hopkins University School of Medicine.
“Once these are settled, then we hope a clinical trial can move forward,” he told MNT.
