The Gary Null Show - 07.15.21

Short chain fatty acids: An 'ace in the hole' against SARS-CoV-2 infection

Scientists find that short chain fatty acids can be used to reduce susceptibility to SARS-CoV-2 infection and mortality from COVID-19

University of Fukui (Japan), July 14, 2021

Humans are no stranger to coronavirus (CoV) pandemics. Just like SARS-CoV-2 (the virus that causes COVID-19), another member of the coronavirus family--SARS-CoV--caused the severe acute respiratory syndrome (SARS) epidemic across parts of Asia in 2003. But, its spread was contained way faster than COVID-19. So, what makes SARS-CoV-2 so contagious?

Both SARS-CoV and SARS-CoV-2 viruses bear "spike proteins" which get inside our cells by binding to a protein called angiotensin-converting enzyme 2 (ACE2) that is found in our cells. However, the SARS-CoV-2 spike (S) protein has been found to have a higher binding affinity (10 to 20 times that of SARS-CoV) to ACE2, thus establishing a link between the pathogen and the protein.

Interestingly, recent studies have shown that patients with COVID-19 who have rhinosinusitis (i.e., inflammation of the nose) have a low risk of hospitalization. Moreover, the expression of ACE2 was reduced in patients with rhinosinusitis. Coincidentally, another study has shown that short-chain fatty acids (SCFAs), produced by bacteria in the gut have beneficial effects in allergy and viral infections. These separate findings prompted an investigation of the effect that SCFAs in the nasal cavity against SARS-CoV-2 infection by scientists from the University of Fukui, Japan, led by Dr. Tetsuji Takabayashi.

In a new study published in the American Journal of Rhinology & Allergy, the scientists attempted to understand the effect of SCFAs on ACE2 expression in the nasal passage, and the potential impact on COVID-19 infection. "This is the first report that short-chain fatty acids (SCFAs) effectively reduce the ACE2 levels in human airway epithelial cells," remarks Dr. Takabayashi.

To understand the status of ACE2 expression in patients with allergies, the researchers studied the levels of ACE2 in the inner lining of the nose in patients with seasonal allergic rhinitis induced by Japanese cedar pollen (SAR-JCP) and chronic rhinosinusitis (CRS). Using techniques like real time-PCR to quantify the expression of ACE2, the researchers found that there was no increase in ACE2 expression in in patients with SAR-JCP, whereas it was decreased in patients with CRS.

To better understand the effect of SCFAs on ACE2 expression, the researchers cultured nasal epithelial cells and exposed them to either SFCA and double-stranded RNA (similar to the nuclear material found in some viruses and known to enhance ACE2 expression). Upon examining the expression of ACE2, the researchers saw that the SFCAs had suppressed ACE2 expression in the presence of the RNA as well.

These results suggest that SFCAs has potential therapeutic applications against COVID-19. Dr. Takabayashi explains, "The nasal mucosa exhibits the highest ACE2 expression among human organs and hence is a prominent target of original infection. Therefore, the development of strategies to downregulate ACE2 expression in nasal epithelial cells could reduce SARS-CoV-2 transmission and be useful as a novel therapeutic approach."

The team's timely findings will certainly aid in our fight against COVID-19.

 

Flavonoids may slow Alzheimer onset

Tufts University Human Nutrition Center, July 13, 2021

The following information was released by the U.S. Department of Agriculture:

According to the U.S. Centers for Disease Control and Prevention, an estimated 5.8 million Americans aged 65 or older live with Alzheimer's disease, and that number is projected to nearly triple by 2160. Fortunately, USDA-funded research may have found a tasty way to slow disease onset.

A study published in the American Journal of Clinical Nutrition suggests that diets high in flavonoids may protect cognitive health. Flavonoids are plant nutrients known for their antioxidant, antiviral, and anticancer properties and are found in berries, tea, dark chocolate, and other foods.

"Alzheimer's disease is a significant public health challenge," said Paul Jacques, nutritional epidemiologist at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University in Boston. "Given the absence of drug treatments, preventing Alzheimer's disease through a healthy diet is an important consideration."

Jacques's study, which followed 2,809 people for nearly 20 years, revealed that diets high in fruits and vegetables showed significant promise to quell the onset of Alzheimer's.

"Our study showed that individuals with the highest intakes of flavonoids were more than 50% less likely to develop Alzheimer's disease, relative to those with the lowest intakes," he said. "Plant foods, such as vegetables, fruits, nuts, and seeds are good sources of flavonoids."

According to Jacques, flavonoid-rich diets help more than just Alzheimer's disease and related dementia.

"The bottom line is that there are many reasons to consume a healthy diet, including lower risks of cardiovascular disease and some cancers. We can now add protection of cognitive health and prevention of Alzheimer's disease to that list."

 

 

Mitochondria malfunction shown to be the major cause of Parkinson's

University of Copenhagen (Denmark), July 9, 2021

12,000 people in Denmark and 7 to 10 million people worldwide suffer from Parkinson's Disease (PD). It is the second most common neurogenerative disorder of aging and the most common movement disorder, but the cause of the disease is largely unknown.

In a new study, researchers from the University of Copenhagen show that the most common form of the disease, encompassing 90 to 95 percent of all Parkinson's Disease cases known as sporadic PD, is caused by a blockage of a pathway that regulates the nerve cell's powerhouse, the mitochondria.

"Just like when people eat, cells take what they need and get rid of the rest waste products. But if our brain cells have this specific kind of signaling blockage, it means that the powerhouse of the cell—mitochondria—cannot get cleaned up after being damaged," explains corresponding author and group leader Professor Shohreh Issazadeh-Navikas at the Biotech Research & Innovation Centre.

The blockage leads to an accumulation of high amounts of damaged mitochondria, while not being able to produce enough energy for the cells. It causes neurons to gradually die, which is the reason for the development of Parkinson's Disease symptoms, and why it leads to dementia.

The blockage is caused by a dysregulation of the immune genes, more specifically a pathway called type 1 interferon, which is normally important for fight against viruses, but now we show that it is also responsible for regulating the energy supply of the nerve cells.

"Every part of our body needs to be regulated. We get a signal to stop eating, when we are full, and the same thing happens everywhere else in our body. If we get an infection, parts of our body need to fight it and stop it from replicating. But when the infection is cleaned up, the signal should subside. This is the job of a protein called PIAS2. That causes the blockage of the type 1 interferon-pathway, and when the infection is over, the blockage should stop and go back to normal. But that does not seem to be the case in patients with Parkinson's Disease. We further demonstrate that this dysregulation leads to a defect in the mitochondrial energy supply, as mentioned before," says Issazadeh-Navikas.

These pathways are very important for brain functions, but they are also associated with microbial and virus recognition. For example, they are very important for fighting COVID-19, and a mutation in the related gene has been shown to be linked to a deadly outcome after contracting COVID-19.

The researchers combined and analyzed four data sets, which studied neurons from brains with Parkinson's Disease and looked at what type of genes they express.

They then looked at which gene patterns were disturbed in patients with Parkinson's Disease and especially those who had also developed PD with dementia.

In order to test the results, the major findings of the combined data was tried in three different mouse models using a negative regulator of the type I interferon pathway, PIAS2, which had been identified from the patients study as one of the key proteins linked to the progression of Parkinson's Disease and dementia.

"We show that a high accumulation of the PIAS2-protein is what is causing the blockage in the pathway, which should have activated the processes responsible for removing damaged protein and mitochondrial garbage," says Issazadeh-Navikas.

"The accumulation of damaged mitochondrial mass further leads to increase of other toxic proteins. So when we compare patients to same-aged healthy patients without Parkinson's Disease, we see that this PIAS2-protein is highly expressed in the neurons, which is why this pathway should be evaluated for potential roles in the other forms of familial Parkinson's Disease that we have not studied here."

The researchers hope the study will encourage research to counteract the pathway blockage, which could have a beneficial impact on the disease and towards preventing dementia.

In the next stages, the Issazadeh-Navikas group will study how the pathwaycontributes to neuronal homeostasis and survival, as well as how its dysregulation causes neuronal cell death.

 

Combining plant-based diet and a healthy microbiome may protect against multiple sclerosis

Metabolism of isoflavone by gut bacteria protects mice from MS-like inflammation

University of Iowa, July 13, 2021

A new University of Iowa study suggests that metabolism of plant-based dietary substances by specific gut bacteria, which are lacking in patients with multiple sclerosis (MS), may provide protection against the disease. 

The study led by Ashutosh Mangalam, PhD, UI associate professor of pathology, shows that a diet rich in isoflavone, a phytoestrogen or plant-based compound that resembles estrogen, protects against multiple sclerosis-like symptoms in a mouse model of the disease. Importantly, the isoflavone diet was only protective when the mice had gut microbes capable of breaking down the isoflavones. The findings were published July 9 in Science Advances.

"Interestingly, previous human studies have demonstrated that patients with multiple sclerosis lack these bacteria compared to individuals without MS," Mangalam says. "Our new study provides evidence that the combination of dietary isoflavones and these isoflavone metabolizing gut bacteria may serve as a potential treatment for MS."

Isoflavones are found in soybeans, peanuts, chickpeas and other legumes. The study also found that mice fed the isoflavone diet have a microbiome that is similar to the microbiome found in healthy people and includes the bacteria which can metabolize isoflavones. Conversely, a diet lacking isoflavones promotes a microbiome in mice which is similar to one observed in patients with MS and lacks beneficial bacteria that can metabolize isoflavone.

Multiple sclerosis is an autoimmune disease of the brain and spinal cord where the immune system attacks the protective coating surrounding nerve fibers. The symptoms of this disease include muscles weakness, balance issues, and problems with vision and thinking. While there are treatments that slow down the disease, there is currently no cure for MS. 

Although the exact cause of MS is unknown, a complex interaction between genetic and environmental factors are thought to initiate the disease. Recently, the gut microbiome--the trillions of gut bacteria the live inside human intestines--has emerged as a potential environmental factor that contributes to MS. In prior work, Mangalam and colleagues demonstrated that there are significant differences between the gut microbes of patients with MS and people without MS. Specifically, patients with MS lacked bacteria that are able to metabolize isoflavones. Although role of gut microbiome in human diseases such as MS is being appreciated, the mechanism through which these gut bacteria might influence the disease is poorly understood.

In the current study, Mangalam's team, including first author Samantha Jensen, a UI graduate student in immunology, found that the bacteria that are lacking in patients with MS are able to suppress inflammation in a mouse model of MS. The team compared the effects of an isoflavone diet and an isoflavone-free diet on disease in the mouse model of MS. They found that the isoflavone diet led to disease protection. However, when the team placed the mice on the isoflavone diet but removed the isoflavone-metabolizing gut bacteria, the isoflavone diet was no longer able to protect against MS-like symptoms. When the bacteria were reintroduced, the protective effect of the isoflavone diet was restored. Furthermore, the team was able to show that a specific isoflavone metabolite called equol, which is produced by the gut bacteria from isoflavone, is also able to provide protection against disease. 

"This study suggests that an isoflavone diet may be protective so long as the isoflavone metabolizing gut bacteria are present in the intestines," say Mangalam, who also is a member of the Iowa Neuroscience institute and Holden Comprehensive Cancer Center.

 

How a Mediterranean diet could reduce osteoporosis

University of East Anglia (UK), July 12, 2021

Eating a Mediterranean-type diet could reduce bone loss in people with osteoporosis - according to new research from the University of East Anglia.

New findings published today show that sticking to a diet rich in fruit, vegetables, nuts, unrefined cereals, olive oil, and fish can reduce hip bone loss within just 12 months.

The study is the first long-term, pan-European clinical trial looking at the impact of a Mediterranean diet on bone health in older adults.

More than 1,000 people aged between 65 and 79 took part in the trial, and volunteers were randomised into two groups - one which followed a Mediterranean diet and a control group which did not.

Bone density was measured at the start and after 12 months. The diet had no discernible impact on participants with normal bone density, but it did have an effect on those with osteoporosis.

People in the control group continued to see the usual age-related decrease in bone density, but those following the diet saw an equivalent increase in bone density in one part of the body - the femoral neck. This is the area which connects the shaft of the thigh bone to its rounded head, which fits in the hip joint.

UK study lead Prof Susan Fairweather-Tait, from UEA's Norwich Medical School, said: "This is a particularly sensitive area for osteoporosis as loss of bone in the femoral neck is often the cause of hip fracture, which is common in elderly people with osteoporosis.

"Bone takes a long time to form, so the 12-month trial, although one of the longest to date, was still a relatively short time frame to show an impact. So the fact we were able to see a marked difference between the groups even in just this one area is significant."

The EU-funded trial, led by the University of Bologna, was completed by 1142 participants recruited across five centres in Italy, the UK, the Netherlands, Poland and France. Those following the Mediterranean diet increased their intake of fruits, vegetables, nuts, unrefined cereals, olive oil, and fish, consumed small quantities of dairy products and meat and had a moderate alcohol intake.

People in the intervention group were provided with foods such as olive oil and wholemeal pasta, to encourage them to stick to the diet, and were also given a small vitamin D supplement, to even out the effects of different levels of sunlight on vitamin D status between the participating countries.

At the start and end of the trial, blood samples were taken to check for circulating biomarkers. Bone density was measured in over 600 participants across both groups at the lumbar spine and femoral neck. Of these participants, just under 10% were found to have osteoporosis at the start of the study.

Co-researcher from UEA, Dr Amy Jennings said: "Although this is a small number it is sufficient for the changes in femoral neck bone density between the two groups to be statistically significant.

"Those with osteoporosis are losing bone at a much faster rate than others, so you are more likely to pick up changes in these volunteers than those losing bone more slowly, as everyone does with age.

"With a longer trial, it's possible we could have picked up changes in the volunteers with normal bone density. However, we already found it quite challenging to encourage our volunteers to change their diet for a year, and a longer trial would have made recruitment more difficult and resulted in a higher drop-out."

The researchers would now like to see a similar, or ideally longer, trial in patients with osteoporosis, to confirm the findings across a larger group and see if the impact can be seen in other areas of the body. If the condition could be mitigated through diet, this would be a welcome addition to current drug treatments for osteoporosis, which can have severe side effects.

But in the meantime, say the researchers, there is no reason for those concerned about the condition not to consider adapting their diet.

"A Mediterranean diet is already proven to have other health benefits, reducing the risk of cardiovascular disease, Parkinson's, Alzheimer's and cancer," said Prof Fairweather-Tait. "So there's no downside to adopting such a diet, whether you have osteoporosis or not."

'A Mediterranean-like dietary pattern with vitamin D3 (10 μg/day) supplements reduced rate of bone loss in older Europeans with osteoporosis at baseline: results of a one year randomised controlled trial' is published in the American Journal of Clinical Nutrition .

 

Rishi mushroom promotes sleep through a gut microbiota-dependent and serotonin-involved pathway 

Hang-zhou Medical College (China), July 10, 2021

According to news reporting out of Zhejiang, People’s Republic of China, research stated, “Ganoderma lucidum is a medicinal mushroom used in traditional Chinese medicine with putative tranquilizing effects. However, the component of G. lucidum that promotes sleep has not been clearly identified.”

Our news journalists obtained a quote from the research from Hangzhou Medical College, “Here, the effect and mechanism of the acidic part of the alcohol extract of G. lucidum mycelia (GLAA) on sleep were studied in mice. Administration of 25, 50 and 100 mg/kg GLAA for 28 days promoted sleep in pentobarbital-treated mice by shortening sleep latency and prolonging sleeping time. GLAA administration increased the levels of the sleep-promoting neurotransmitter 5-hydroxytryptamine and the Tph2, Iptr3 and Gng13 transcripts in the sleep-regulating serotonergic synapse pathway in the hypothalamus during this process. Moreover, GLAA administration reduced lipopolysaccharide and raised peptidoglycan levels in serum. GLAA-enriched gut bacteria and metabolites, including Bifidobacterium, Bifidobacterium animalis, indole-3-carboxylic acid and acetylphosphate were negatively correlated with sleep latency and positively correlated with sleeping time and the hypothalamus 5-hydroxytryptamine concentration. Both the GLAA sleep promotion effect and the altered faecal metabolites correlated with sleep behaviours disappeared after gut microbiota depletion with antibiotics.”

According to the news editors, the research concluded: “Our results showed that GLAA promotes sleep through a gut microbiota-dependent and serotonin-associated pathway in mice.”

 

 

Vitamin C found to block growth of cancer stem cells, says peer reviewed study

University of Salford (UK),  July 8, 2021

 

Increasingly, researchers are discovering the role played by cancer stem cells in the growth and spread of the disease. In groundbreaking new research, vitamin C showed its ability to target cancer stem cells and stop their growth – preventing the recurrence of tumors.

Although mainstream medicine has been slow to accept the cancer-fighting properties of vitamin C, the exciting results of this study could help to change that.

In a newly-published study conducted at the University of Salford in Manchester, vitamin C demonstrated its power to stop tumors in their tracks by interfering with cancer stem cell metabolism – suppressing their ability to process energy for survival and growth.

Cancer stem cells are responsible for triggering tumor recurrence, and promoting their growth and metastasis. Researchers believe that cancer stem cells give cancer its ability to resist chemotherapy and radiation – the reason for treatment failure in advanced cancer patients.

The study, helmed by researchers Michael P. Lisanti and Gloria Bonucelli, was published last month in Oncotarget, a peer-reviewed journal. Peer-reviewed studies are considered the gold standard of scientific research.

The study was the first to explore the effects of vitamin C on cancer stem cells – and provided the first evidence that vitamin C, in the form of ascorbic acid, can target and kill them.

In a side-by-side comparison of seven different substances, vitamin C even outperformed an experimental cancer drug.

The team investigated the impact on cancer stem cells of seven different substances. Three were natural substances, three were experimental drugs, and one was an FDA-approved clinical drug that is widely used.

The natural products studied, along with vitamin C, were silibinin – derived from milk thistle seeds – and caffeic acid phenyl ester – or CAPE – derived from honeybee propolis. The experimental drugs were actinonin, FK866 and 2-DG, and the clinical drug was stiripentol.

Researchers noted that vitamin C destroyed cancer stem cells by inducing oxidative stress. And, the vitamin performed this process ten times more effectively than 2-DG.

Vitamin C used two different mechanisms of action to attack cancer stem cells. It worked as a pro-oxidant in cancer cells, depleting them of the antioxidant glutathione and causing oxidative stress and apoptosis – or cell death. It also inhibited glycolysis, which is the process that creates energy production in cell mitochondria.

By inhibiting glycolysis, vitamin C inhibited mitrochondrial protein synthesis in cancer stem cells – while leaving healthy cells unaffected.

Both experimental and approved cancer drugs can feature serious adverse effects, including thrombocytopenia – a deficiency of platelets in the blood that can cause bruising and slow blood clotting. They can also induce lymphopenia – a decrease in the body’s infection-fighting white blood cells – and anemia, or low red blood cells.

And the clinically-approved drug used in the study, stiripentol, can cause severe nausea, vomiting and fatigue.
On the other hand, the National Cancer Center reports that high-dose vitamin C has caused very few side effects when used in clinical studies.

All seven of the substances tested inhibited the growth of cancer cells to varying degrees – including the non-toxic natural substances. But researchers said the most “exciting” results were with vitamin C.

The research team concluded that vitamin C was a “promising new agent,” and called for more study to explore its use as an adjunct to conventional cancer therapies to prevent tumor recurrence and growth.

“Vitamin C is cheap, natural, non-toxic and readily available, so to have it as a potential weapon in the fight against cancer would be a significant step,” observed Dr. Lisanti.

As in most of the successful studies showing vitamin C’s cancer-fighting properties, researchers used high doses of vitamin C, administered intravenously. IV vitamin C therapy is available in some alternative and holistic cancer treatment clinics worldwide.

Again, vitamin C was 1,000 percent more effective than 2-DG, an experimental pharmaceutical drug – in targeting cancer stem cells. If vitamin C were developed by big pharma, these results would be shouted from the rooftops and featured in newspaper headlines.

Yet, as always, “the powers that be” in mainstream medicine respond with…crickets.

The reason; say natural health experts, is all too obvious. As a natural nutrient and vitamin, vitamin C can’t be patented, and is inexpensive and easy to obtain. Therefore, there is no incentive for cancer clinics to promote it – when they can instead rake in the profits from chemotherapy.

The indifference of conventional medicine to vitamin C is all the more frustrating because the nutrient has been shown to be an effective and non-toxic anti-cancer agent in previous studies, including many conducted by Nobel prize-winning scientist Linus Pauling. Vitamin C has been shown in a Japanese study to cut mortality in cancer patients by 25 percent. In addition, it has inhibited tumors in animal studies, and been shown to kill cancer cells in a wide variety of cancer cell lines.

How much longer will the potential of this safe and powerful cancer-fighting nutrient be overlooked?