The Gary Null Show - 03.16.21

Ginger compound shows bone-protective properties

Mie University (Japan), March 15, 2021

According to news originating from Tsu, Japan, research stated, “Osteoporosis is the most common aging-associated bone disease and is caused by hyperactivation of osteoclastic activity. We previously reported that the hexane extract of ginger rhizome [ginger hexane extract (GHE)] could suppress receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclastogenesis in RAW264.7 cells.”

Our news correspondents obtained a quote from the research from Mie University: “However, the anti-osteoclastic components in GHE have not yet been identified. In this study, we separated GHE into several fractions using silica gel column chromatography and evaluated their effects on osteoclastogenesis using a RAW264.7 cell osteoclast differentiation assay (in vitro) and the zebrafish scale model of osteoporosis (in vivo). We identified that the fractions containing 10-gingerol suppressed osteoclastogenesis in RAW264.7 cells detected by tartrate-resistant acid phosphatase (TRAP) staining. In zebrafish, GHE and 10-gingerol suppressed osteoclastogenesis in prednisolone-induced osteoporosis regenerated scales to promote normal regeneration. Gene expression analysis revealed that 10-gingerol suppressed osteoclast markers in RAW264.7 cells [osteoclast-associated immunoglobulin-like receptor, dendrocyte-expressed seven transmembrane protein, and matrix metallopeptidase-9 (Mmp9)] and zebrafish scales [osteoclast-specific cathepsin K (CTSK), mmp2, and mmp9]. Interestingly, nuclear factor of activated T-cells cytoplasmic 1, a master transcription regulator of osteoclast differentiation upstream of the osteoclastic activators, was downregulated in zebrafish scales but showed no alteration in RAW264.7 cells.”

According to the news reporters, the research concluded: “In addition, 10-gingerol inhibited CTSK activity under cell-free conditions. This is the first study, to our knowledge, that has found that 10-gingerol in GHE could suppress osteoclastic activity in both in vitro and in vivo conditions.”

 

 

Mindfulness meditation improves quality of life in heart attack survivors

Hacettepe University (Turkey), March 10, 2021

An eight-week programme of mindfulness meditation improves quality of life and reduces fear of activity in heart attack patients, according to research presented today at ESC Acute CardioVascular Care 2021, an online scientific congress of the European Society of Cardiology (ESC).1

"A heart attack is a serious life-threatening event and survivors can suffer from low quality of life," said study author Dr. Canan Karadas of Hacettepe University, Ankara, Turkey. "One reason is a fear of movement, called kinesiophobia, which limits daily activity due to concerns of another heart attack."

"Mindfulness refers to the mental state achieved by focusing awareness on the present moment, including thoughts, feelings, and physical sensations," continued Dr. Karadas. "It has drawn increasing attention for treating chronic conditions such as high blood pressure. Our study examined its effect on fatigue, kinesiophobia, and quality of life after an acute myocardial infarction."

The study included 56 patients who had experienced a heart attack. The average age at enrolment was 55 years. Participants were randomly assigned to a mindfulness or control group for eight weeks. Patients in the control group attended one 15-minute individual education session on the structure and function of the heart, the coronary arteries, and diseases of the heart. 

Patients assigned to the mindfulness intervention attended an individual session which included a 15-minute description of the technique. This was followed by 15 minutes of supervised practice: patients were asked to sit comfortably on a chair with their backs straight and eyes closed. They were then instructed to breathe deeply - inhaling through the nose and exhaling through the mouth using the diaphragm - and focus on their breathing and the present moment. Participants received a recording of the instructions via WhatsApp and were asked to repeat the 15-minute session every day at home in a quiet room. Daily reminders (text messages or phone calls) were used to motivate patients to practice the meditation and to evaluate their compliance with the study protocol.

Fatigue, kinesiophobia, and quality of life were assessed at baseline and weeks four, eight and 12 using the Piper Fatigue Scale, Tampa Scale for Kinesiophobia Heart questionnaire, and MacNew Heart Disease Health-Related Quality of Life questionnaire which examines patients' feelings about how their heart condition affects daily function overall and in three areas (physically, emotionally, and socially).

At baseline, there were no differences in the three variables between the intervention and control groups. By week four, patients in the mindfulness group had less fear of movement compared to the control group - a benefit that was sustained at weeks eight and 12. Patients in the mindfulness group had better quality of life overall and in all three areas than those in the control group at week eight, while at week 12 they continued to report better emotional function. Measurements of fatigue did not vary between the two groups at any time point.

Dr. Karadas noted that participants only reported mild fatigue at the beginning of the study which may explain why meditation did not have any impact.

She said: "Our study shows that mindfulness can reduce fear of movement and improve quality of life in heart attack survivors, with effects extending beyond the completion of the intervention. One explanation may be that meditation replaces catastrophic thinking with positive thoughts, making patients feel less emotionally and physically vulnerable. The findings suggest that mindfulness may be considered in the rehabilitation of patients after a heart attack. These results are very encouraging but more studies are needed to confirm our findings."

 

 

This TCM formula alters brain pathways to alleviate anxiety-like behavior

Beijing University of Chinese Medicine, March 11, 2021

In a recent study, researchers at Beijing University of Chinese Medicine found that a traditional Chinese medicine (TCM) formula known as xiao yao san (XYS) can alleviate anxiety-like behaviors in rats. They reported that XYS exerts its effects by altering the expression of genes involved in the c-Jun N-terminal kinase (JNK) signaling pathway. This pathway plays a role in the induction of chronic stress.

The researchers reported their findings in an article published in the journal Biological and Pharmaceutical Bulletin.

XYS is an effective treatment for anxiety

Xiao yao san means happy, carefree powder in TCM. Its most well-known use is as a treatment for menopausal anxiety and depression. Some reports also suggest that when combined with acupuncture and moxibustion, XYS relieves anxiety and depressionfollowing procedures such as placenta transplantation and test tube fertilization.

According to TCM records, XYS is composed of eight different medicinal herbs, namely, Bupleurum chinense (Chinese thorow wax, chai hu), Angelica sinensis (female ginseng, dang gui), Paeonia lactiflora (white peony, bai shao), Atractylodes macrocephala (white atractylodes, bai zhu), Poria cocos (poria mushroom, fu ling), Zingiber officinale (ginger, sheng jiang), Mentha piperita (Chinese peppermint, bo he) and Glycyrrhiza uralensis(licorice, gan cao). Several clinical trials have found that the combination of these TCM herbs is more powerful than modern antidepressants.

In their previous study, the researchers reported that XYS exerts anxiolytic effects in ratssubjected to two weeks of chronic immobilization stress (CIS). They hypothesized that these effects may be attributed to the influence of XYS on JNK, a stress-activated enzyme. Different types of stressors are known to activate the JNK signaling pathway, which can ultimately lead to cell damage and apoptosis.

To test their hypothesis, the researchers employed 40 rats and divided them into five groups: the control group, which received deionized water; the model group, which also received deionized water; the SP600125 group, which underwent surgery; the per se group, which also underwent surgery; and the XYS group, which received 3.9 g/kg XYS daily.

The researchers injected 1 percent dimethyl sulfoxide (DMSO) citrate buffer solution and SP600125 separately and bilaterally into the rats (via the brain’s ventricular system) in the two surgery groups. They then subjected all the groups except for the control to 14 days of CIS. 

On Day 15, the researchers measured the bodyweight of the rats and subjected the animals to the elevated plus maze (EPM) and novelty suppressed feeding (NSF) tests. They then examined JNK signaling pathway indices, including phosphorylated JNK (P-JNK), JNK, phosphorylated c-Jun (P-c-Jun) and cytochrome C (cyt-C). The release of cyt-C into the cytosol of cells is said to trigger programmed cell death, or apoptosis.

Based on body weight and behavioral analyses of the model rats, the researchers confirmed the successful induction of anxiety-like behaviors in the animals. They reported that CIS altered the expression of P-JNK, JNK and P-c-Jun in the hippocampus of the model rats. However, treatment with XYS and SP600125, a known JNK inhibitor, for 14 days changed rat body weight and behaviors, along with P-JNK, JNK and P-c-Jun expression levels, for the better. Both XYS and SP600125 had no effect on cyt-C.

These results suggest that XYS reduces anxiety-like behaviors induced by CIS by inhibiting JNK signaling in the hippocampus.

 

 

Electricity could help speed wound healing, new study shows

Electrical impulses may help vessels more quickly get healing agents to injuries

Ohio State University, March 11, 2021

Electric stimulation may be able to help blood vessels carry white blood cells and oxygen to wounds, speeding healing, a new study suggests.

The study, published in the Royal Society of Chemistry journal Lab on a Chip, found that steady electrical stimulation generates increased permeability across blood vessels, providing new insight into the ways new blood vessels might grow. 

The electrical stimulation provided a constant voltage with an accompanying electric current in the presence of fluid flow. The findings indicate that stimulation increases permeability of the blood vessel - an important characteristic that can help wound-healing substances in the blood reach injuries more efficiently.

"There was this speculation that blood vessels could grow better if you stimulated them electrically," said Shaurya Prakash, senior author of the study and associate professor of mechanical and aerospace engineering at The Ohio State University. "And we found that the response of the cells in our blood vessel models shows significant promise towards changing the permeability of the vessels that can have positive outcomes for our ongoing work in wound healing." 

Blood vessels are crucial for wound healing: They thread throughout your body, carrying nutrients, cells and chemicals that can help control inflammation caused by an injury. Oxygen and white blood cells - which protect the body from foreign invaders - are two key components delivered by blood vessels.

But when there is an injury - for example, a cut on your finger - the architecture of the blood vessels at the wound site are disrupted. That also interrupts the vessels' ability to help the wound heal. Blood vessels regrow on their own, almost like the branches of trees, without external sources of electricity, as part of the healing process.

"And as the blood vessels begin to grow, they replenish the skin and cells and establish a healing barrier again," Prakash said. "But our question was: How do you make this process better and faster, and is there any benefit to doing that?"

What they found, in laboratory tests performed using human cells, is that stimulating blood vessels with electricity showed a marked increase in blood vessel permeability, which is a physical marker suggestive of possible new vessel growth. 

"These initial findings are exciting, and the next phase of the work will require us to study if and how we can actually grow new vessels," Prakash said.

Jon Song, co-author of the paper and associate professor of mechanical and aerospace engineering at Ohio State, said the results imply that one of the primary ways blood vessels work to heal injuries is by allowing molecules and cells to move across the vessels' walls.

"And now we have better understanding for how electric stimulation can change the permeability across the vessel walls," Song said. "Let's say you have a cutaneous wound, like a paper cut, and your blood vessels are severed and that's why you have blood leaking out. What you need is a bunch of bloodborne cells to come to that place and exit out the blood vessel to initiate the wound repair."

The study suggested that changes in blood vessel permeability could get those bloodborne cells to a wound site more quickly, though it did not explain the reasons why that happened. The study seemed to indicate that electricity affected the proteins that hold blood vessel cells together, but those results were not conclusive.

The study is an extension of work by a broader team, led by Prakash, that previously showed electric bandages could help stimulate healing in wounded dogs. That work indicated that electrical stimulation might also help manage infections at wound sites - a phenomenon the researchers also hope to research further.

 

 

Lower risk of brain injury for at-risk infants whose mothers consumed pomegranate juice

Preliminary findings from a randomized controlled trial suggest pomegranate juice may provide neuroprotection in pregnancies with intrauterine growth restriction

Brigham and Women's Hospital, March 11, 2021

Intrauterine growth restriction (IUGR) is common and concerning, but few therapeutic options exist for pregnant mothers who receive this diagnosis. IUGR is a condition in which a baby in the womb is measuring small for its gestational age, often because of issues with the placenta, resulting in compromised or insufficient transfer of oxygen and nutrients to the growing fetus. The developing fetal brain is particularly vulnerable to these effects. One out of every 10 babies is diagnosed with IUGR, and infants with IUGR are at increased risk of death and neurodevelopmental impairment. Recent research on polyphenol-rich pomegranate juice has suggested that it may help protect the brain from injury. In an exploratory, randomized, controlled clinical trial, supported by philanthropic funding and a gift from POM Wonderful, the largest grower and producer of fresh pomegranates and pomegranate juice in the United States, investigators at Brigham and Women's Hospital enrolled pregnant mothers whose infants were diagnosed with IUGR. The team found evidence that drinking pomegranate juice daily may reduce risk of brain injury in IUGR infants, especially during the third trimester when the infant brain may be particularly vulnerable. Findings are published in Scientific Reports.

"There are dietary factors that may influence neuroprotection, especially in high-risk settings such as during labor and delivery," said co-author Terrie Inder, MBCHB, chair of the Department of Pediatric Newborn Medicine at the Brigham. "We were intrigued by findings from preclinical research suggesting that polyphenols, which are found at high concentrations in pomegranate juice, might be highly protective. Our clinical trial provides the most promising evidence to date that polyphenols may provide protection from risk of brain injury in IUGR infants."

"While exploratory, our results are promising and suggest that being able to intervene before birth may aid in protecting the newborn brain from the devastating effects of brain injury," said corresponding author Lillian G. Matthews, PhD, a neuroscientist at Monash Biomedical Imaging and Turner Institute for Brain and Mental Health in Australia. Prior to joining Monash, Matthews was at Harvard Medical School and the Brigham in the Department of Pediatric and Newborn Medicine, where she maintains a current affiliation.

Polyphenols are part of a class of antioxidants found in certain foods and beverages, including almonds, berries, red wine and teas. Pomegranate juice is a particularly rich source of these molecules. Polyphenols are known to cross the blood-brain barrier, and studies in animal models have demonstrated protective effects against neurodegenerative diseases.

For their clinical trial, Inder and colleagues recruited 99 pregnant mothers at the Brigham. The participants were randomly assigned to consume either 8 ounces of pomegranate juice or a polyphenol-free beverage matched for color, taste and calorie-count. Participants drank the juice daily from the time of enrollment until delivery. 

The team performed fetal MRI measurements on approximately half of the participants prior to mothers starting the juice regimen and found no evidence of fetal brain injury at that time. After delivery, neonatal MRI measurements showed that infants whose mothers consumed pomegranate juice were less likely to have brain injury compared to those randomized to placebo. Infants had lower risk of cortical grey matter injury and white matter injury. The team also found no evidence of ductal constriction, a potential safety concern. 

Given the exploratory nature of the study and its limited size, the authors caution that larger controlled trials are needed. The team also plans to continue studying infants enrolled in their study over the next 2-3 years to assess the infants' neurodevelopmental outcome. 

"Our neurodevelopmental follow-up studies are ongoing, and we encourage other investigators studying high-risk infant populations to consider the influence of polyphenols for neuroprotection," said Inder. "My dream is that we will one day be able to offer women a way to help shield their infant's brain from potential injury. In the meantime, we'll continue to follow participants to provide further insight into the potential clinical implications of prenatal pomegranate juice."

 

Topical curcumin gel effective in treating burns and scalds

David Geffen School of Medicine, March 14, 2021

 

What is the effect of Topical Curcumin Gel for treating burns and scalds? In a recent research paper, published in the open access journal BioDiscovery, Dr. Madalene Heng, Clinical Professor of Dermatology at the David Geffen School of Medicine, stresses that use of topical curcumin gel for treating skin problems, like burns and scalds, is very different, and appears to work more effectively, when compared to taking curcumin tablets by mouth for other conditions.

 

"Curcumin gel appears to work much better when used on the skin because the gel preparation allows curcumin to penetrate the skin, inhibit phosphorylase kinase and reduce inflammation," explains Dr Heng.

 

In this report, use of curcumin after burns and scalds were found to reduce the severity of the injury, lessen pain and inflammation, and improve healing with less than expected scarring, or even no scarring, of the affected skin. Dr. Heng reports her experience using curcumin gel on such injuries using three examples of patients treated after burns and scalds, and provides a detailed explanation why topical curcumin may work on such injuries.

 

Curcumin is an ingredient found in the common spice turmeric. Turmeric has been used as a spice for centuries in many Eastern countries and gives well known dishes, such as curry, their typical yellow-gold color. The spice has also been used for cosmetic and medical purposes for just as long in these countries.

 

In recent years, the medicinal value of curcumin has been the subject of intense scientific studies, with publication numbering in the thousands, looking into the possible beneficial effects of this natural product on many kinds of affliction in humans.

 

This study published reports that topical curcumin gel applied soon after mild to moderate burns and scalds appears to be remarkably effective in relieving symptoms and improved healing of the affected skin.

 

"When taken by mouth, curcumin is very poorly absorbed into the body, and may not work as well," notes Dr. Heng. "Nonetheless, our tests have shown that when the substance is used in a topical gel, the effect is notable."

 

The author of the study believes that the effectiveness of curcumin gel on the skin - or topical curcumin - is related to its potent anti-inflammatory activity. Based on studies that she has done both in the laboratory and in patients over 25 years, the key to curcumin's effectiveness on burns and scalds is that it is a natural inhibitor of an enzyme called phosphorylase kinase.

 

This enzyme in humans has many important functions, including its involvement in wound healing. Wound healing is the vital process that enables healing of tissues after injury. The process goes through a sequence of acute and chronic inflammatory events, during which there is redness, swelling, pain and then healing, often with scarring in the case of burns and scalds of the skin. The sequence is started by the release of phosphorylase kinase about 5 mins after injury, which activates over 200 genes that are involved in wound healing.

 

Dr. Heng uses curcumin gel for burns, scalds and other skin conditions as complementary treatment, in addition to standard treatment usually recommended for such conditions.

 

 

Psychedelic science holds promise for mainstream medicine

University of Nevada, March 10, 2021

Psychedelic healing may sound like a fad from the Woodstock era, but it's a field of study that's gaining traction in the medical community as an effective treatment option for a growing number of mental health conditions.

While the study of psychedelics as medicine is inching toward the mainstream, it still remains somewhat controversial. Psychedelics have struggled to shake a 'counterculture' perception that was born in the 1960s, a view that had stymied scientific study of them for more than 50 years. 

But that perception is slowly changing.

Mounting research suggests that controlled treatment with psychedelics like psilocybin mushrooms, LSD, and MDMA—better known as ecstasy—may be effective options for people suffering from PTSD, anxiety disorders, and depression. The U.S. Food & Drug Administration recently granted 'breakthrough therapy' status to study the medical benefits of psychedelics. And two years ago this month, the FDA approved a psychedelic drug—esketamine—to treat depression. 

An increasing number of states and municipalities are also grappling with calls to decriminalize psychedelic drugs, a move that UNLV neuroscientist Dustin Hines says could further the recent renaissance in psychedelic science. 

"The resurgence in interest in psychedelic medicine is likely related to multiple factors, including decreasing societal stigma regarding drugs like hallucinogens and cannabis, increasing awareness of the potential therapeutic compounds found naturally occurring in plants and fungi, and the growing mental health crisis our nation faces," says Hines. "Because of the intersection between the great need for innovation and wider social acceptance, researchers have started to explore psychedelics as novel treatments for depressive disorders, including work with compounds that have been used for millennia." 

In the Hines lab at UNLV, husband and wife researchers Dustin and Rochelle Hines are uncovering how psychedelics affect brain activity. Their work, published recently in Nature: Scientific Reports, shows a strong connection in rodent models between brain activity and behaviors resulting from psychedelic treatment, a step forward in the quest to better understand their potential therapeutic effects. 

We caught up with the Hineses to learn more about the evolution of psychedelic science—which actually dates back thousands of years—their research (which doesn't date back as long), misconceptions about this emerging field of study, and what to expect next.

The scientific study of psychedelics holds great promise for people suffering with mental illness. Where do we stand?

Dustin Hines: It's estimated that 1 in 5 American adults suffer from some type of mental illness. And while not all require pharmacological treatment, unfortunately there's been limited progress in advancing novel therapies for depressive disorders in 50 or more years. 

Rochelle Hines: It's also worth noting that available therapies for major depression are only effective in specific segments of the depressed population. That's what makes the study of psychedelic compounds so fascinating. Recent clinical studies have empirically demonstrated that these compounds can exert rapid antidepressant effects—essentially bringing into the clinic a practice that Mesoamerican and other cultures have used for thousands of years. But there are still quite a few regulatory barriers that limit even research use of psychedelics. We're hopeful that as the public view of psychedelic compounds changes, so too will the federal regulations that currently govern their study.

Current therapies for mental health disorders can take weeks to become effective. Recent research, including your own, shows the potential for psychedelic compounds to work much more quickly. What do we know about how this happens?

Rochelle: Clinical research on the use of psychedelics as therapeutics suggests that they work by altering the connectivity, or communication, between brain regions. Multiple studies suggest that the connectivity of cortical sensory regions and other brain areas is strengthened. Studies have also reported alterations in the patterns of brain activity during psychedelic treatment in patients with depression. 

Dustin: Our recent studies support the evidence for changes in patterns of brain activity, and provide additional detail into specific patterns of brain activity that are generated during psychedelic treatment. The brain activity patterns that we've characterized are related to specific behaviors known to occur following treatment with psychedelic hallucinogens. These findings support the idea that generation of specific brain activity patterns may be a key aspect of the beneficial effects that psychedelic compounds exert.

In your research, you discuss the long history of hallucinogens for ritualistic practices. What did these cultures know that we don't, and how does your work draw upon this ancient evidence?

Rochelle: Modern medicine—which includes our research team—is reinvestigating psychedelic practices with a 5,000-plus year history. Mesoamerican practitioners are known to engage in specific processes that were honed over millennia of skilled use, often including the addition of nicotine to their ritualistic and therapeutic practices with psychedelics. At present, very little research has investigated the synergistic effects of psychedelics and nicotine. 

Dustin: Despite this long history and recent clinical promise, we still really don't know just how these drugs actually work on the brain to influence mood. This knowledge is essential to optimize their therapeutic potential. In our study of brain activity in a rodent model, we found that nicotine enhanced both the brain's slow waveform as well as behavioral arrest, both hallmark aspects of the response to psychedelic hallucinogens. We're now working on studies examining the synergy between psychedelics and nicotine, and whether nicotine enhances the anti-depressant effects of psychedelics. 

Rochelle: We're also investigating the cellular and molecular mechanisms that underlie the specific changes in brain activity following treatment with psychedelics. With this understanding, we may be able to further refine the clinical utility, applicability, and efficacy of psychedelic hallucinogens as medicines.

As researchers who study the possible therapeutic benefits of psychedelics, what are some of the biggest misconceptions you've encountered? How can further scientific study combat them? 

Dustin: Microdosing of psychedelics—where users gain benefit, though not the prototypical "high" from small amounts the drugs is a practice that's been in the news a lot lately. While there are some data suggesting that low doses can exert beneficial effects, the idea that a person can purchase controlled substances without clarity on the content of psychoactive ingredients and regulate their own dosing with precision is in my opinion misguided. By conducting research to examine both purified and synthetic compounds, we can more accurately establish dosing. 

Rochelle: There's a long-standing belief that these drugs are addictive. However, much of the research suggests that these drugs don't result in maladaptive patterns of substance use behavior. To the contrary, some research actually suggests that these compounds may be effective in treating substance use disorders. More research on the effects of these compounds in models may provide better clarity on not only the acute effects, but the effects of repeated dosing. 

Dustin: An important point to drive home with all of this is that psychedelics are powerful psychoactive drugs, and they should not be used for therapeutic purposes without an experienced practitioner. 

The context surrounding the use of psychedelics as a therapy is emerging, but further research into the clinical use of psychedelics is needed to establish procedures and protocols that we hope will ultimately support positive outcomes for patients.