A New Study Supports Others that Showed Games can Slow Cognitive Dysfunction and Improve Quality of Life in the Elderly

According to Medscape News in Playing Board Games May Slow Cognitive Decline, Improve QoL published on October 20, 2023, a new study showed board games can slow cognitive decline. As the study points out it depends on the game, but this study supports other studies that games and the socialization that goes along with them has healthy and "happy" benefits and improves quality of life. "For patients who are elderly and suffer from social isolation and mild cognitive issues, I would definitely recommend board games," study investigator Frederico Emanuele Pozzi, MD, a neurology resident at Fondazione IRCCS San Gerardo dei Tintori in Monza, Italy, told Medscape Medical News. 

Generally, the study in the Journal of Alzheimer's Disease found that board games can improve mental function, executive functions, and quality of life in elderly subjects. Games like Ska, Go, and Mahjong improved cognitive functions, while Mahjong temporarily improved depressive symptoms. The researcher's stated that conventional board games might require a high level of competence involving multiple cognitive processes in various areas. As a result, they might serve as useful cognitive therapies for the elderly population, whether or not they have dementia or Alzheimer's disease." The researcher's goal was "to conduct a systematic review on traditional board games and dementia in order to confirm the theory that these games can either prevent or delay cognitive decline." (Pozzi) What the study demonstrated was that different games affect different regions of the brain but had an overall, benefit for maintaining cognition. 

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Pozzi FE, Appollonio I, Ferrarese C, Tremolizzo L. Can Traditional Board Games Prevent or Slow Down Cognitive Impairment? A Systematic Review and Meta-Analysis. J Alzheimers Dis. 2023;95(3):829-845. doi: 10.3233/JAD-230473. PMID: 37638443.

Long Covid Studies in Preprint

 The study suggests that COVID-19-induced inflammation in the brain, specifically microglia, could lead to glio-vascular failure, a common contributor to various neurological abnormalities. The researchers developed an autopsy platform to integrate molecular anatomy, protein, and mRNA data from brain and peripheral organ samples. They found distinct mechanisms of microglial dysfunction associated with cerebral SARS-CoV-2 infection, including focal loss of microglial P2Y12R, dysregulated interactions, and mitochondrial failure.Infection-induced vascular inflammation in COVID-19 links focal microglial dysfunction with neuropathologies through IL-1/IL-6-related systemic inflammatory states | bioRxiv  

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The COVID-19 pandemic has led to a public health crisis known as post-acute sequelae of COVID-19 (PASC). A study found increased neuroinflammation in PASC individuals compared to healthy controls. Additionally, peripheral blood plasma from PASC individuals showed positive correlations with circulating analytes related to vascular dysfunction. These findings suggest an interaction between neuroinflammation and vascular health may contribute to common symptoms of PASC. Neuroinflammation in post-acute sequelae of COVID-19 (PASC) as assessed by [11C]PBR28 PET correlates with vascular disease measures | bioRxiv  

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Pericytes stabilize blood vessels, but pro-inflammatory conditions may expose perivascular cells to SARS-CoV-2. Engineered pericyte-supported capillaries showed higher extravasation and binding of spike protein in inflamed vessels, suggesting a potential COVID-19 vascular complications target. Vascular inflammation exposes perivascular cells to SARS-CoV-2 infection | bioRxiv  

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A study comparing COVID-19 and neurologic complications found significant network-based relationships between the virus and neuroinflammation and brain microvascular injury pathways implicated in Alzheimer's disease (AD). The study also found aberrant expression of AD biomarkers in cerebrospinal fluid and blood of patients with COVID-19. While transcriptomic analyses showed low expression of SARS-CoV-2 entry factors in the human brain, neuroinflammatory changes were pronounced. The study suggests a possible role for brain microvascular injury in COVID-19-mediated cognitive impairment, with individuals with the AD risk allele showing reduced levels of antiviral defense genes.  Network medicine links SARS-CoV-2/COVID-19 infection to brain microvascular injury and neuroinflammation in dementia-like cognitive impairment | bioRxiv

The Hidden Link Between Inflammation and Disease

What is Parasthesia in Chronic Fatigue Syndrome and Fibromyalgia?

Paresthesia is a term that describes abnormal sensations such as tingling, crawling, itching, numbness, and prickling. These sensations are not painful in most cases, but they can be uncomfortable and bothersome. Paresthesia is a common symptom of chronic fatigue syndrome (CFS) and fibromyalgia, two conditions that affect the nervous system and cause widespread pain and fatigue.

The exact causes of paresthesia in CFS and fibromyalgia are not well understood, but they may involve:

- Damage or pressure on the peripheral nerves (those in the arms and legs) due to inflammation, injury, or chemotherapy

- Immune system changes that affect the nerve function and increase inflammation

- Stress system changes that alter the pain perception and sensitivity

- Energy production changes that impair the cellular function and metabolism

- Genetic factors that predispose to nerve disorders

Parasthesia can occur anywhere in the body, but it is more common in the feet, hands, and face. It can come and go without warning or be triggered by fatigue, stress, illness, or sensory overload. It can also vary in severity and frequency among different people.

Paresthesia can be treated with medications that target the nerve pain, such as antidepressants, anticonvulsants, or opioids. Non-pharmacological treatments include acupuncture, massage, physical therapy, transcutaneous electrical nerve stimulation (TENS), or cognitive-behavioral therapy (CBT). Lifestyle changes such as quitting smoking, exercising regularly, managing stress, and avoiding triggers may also help reduce the occurrence and intensity of paresthesia.

References:

- Paresthesia in Fibromyalgia and Chronic Fatigue Syndrome 

- Chronic Fatigue Syndrome vs Fibromyalgia: How to Tell Them Apart 

- Extreme Itch in Fibromyalgia and Chronic Fatigue Syndrome 

Links:

: https://www.verywellhealth.com/odd-nerve-sensations-chronic-fatigue-syndrome-3972955

: https://www.verywellhealth.com/chronic-fatigue-syndrome-vs-fibromyalgia-5213420

: https://www.verywellhealth.com/extreme-itch-in-fibromyalgia-chronic-fatigue-syndrome-3972965

Does the CLOCK Gene Decrease with Age and what does it have to do with Chronic Fatigue Syndrome and NRF2?

The CLOCK gene is one of the key components of the circadian rhythm, which regulates the biological processes in the body according to the day-night cycle. The circadian rhythm is closely linked to the cellular metabolism and the oxidative stress response, which are both important factors in chronic fatigue syndrome (CFS) and the activation of the Nrf2 pathway.

CFS is a complex disorder characterized by persistent and unexplained fatigue, pain, cognitive impairment and post-exertional malaise. The exact causes of CFS are not well understood, but some studies have suggested that it may be triggered by viral infections, immune dysfunctions, mitochondrial defects or environmental stressors. 

The Nrf2 pathway is a major defense mechanism against oxidative stress, which is caused by an imbalance between the production and elimination of reactive oxygen species (ROS). ROS are normal by-products of cellular metabolism, but they can also damage the DNA, proteins and lipids in the cells if not properly controlled. The Nrf2 pathway regulates the expression of several genes that encode for antioxidant enzymes, detoxification proteins and anti-inflammatory molecules.

The CLOCK gene may influence both CFS and the Nrf2 pathway through its role in regulating the circadian rhythm. The circadian rhythm affects the levels of different molecules in the cell, including ROS and Nrf2. Disruption of the circadian rhythm can lead to increased oxidative stress, inflammation and metabolic disturbances, which may contribute to the development or worsening of CFS symptoms. The CLOCK gene may decrease with age and may be one factor why CFS develops in many patients as they age.  Moreover, some studies have shown that the CLOCK gene itself can modulate the Nrf2 pathway by directly binding to its promoter region and enhancing its transcription.

However, the relationship between the CLOCK gene, CFS and the Nrf2 pathway is not straightforward and may depend on several factors, such as genetic variations, environmental exposures and disease stages. For example, some studies have reported that certain SNPs in the CLOCK gene are associated with increased risk or severity of CFS, while others have found no significant association. Similarly, some studies have suggested that Nrf2 activation may have beneficial effects for CFS patients by reducing oxidative stress and inflammation, while others have proposed that Nrf2 overactivation may be detrimental by inducing drug resistance and tumor development.

Therefore, more research is needed to elucidate the molecular mechanisms and clinical implications of the interactions between the CLOCK gene, CFS and the Nrf2 pathway. Understanding these interactions may help to identify novel biomarkers, diagnostic criteria and therapeutic targets for CFS patients.

References:

: https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-022-03815-8

: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5610158/

: https://www.frontiersin.org/articles/10.3389/fphys.2021.727806/full

: https://www.frontiersin.org/articles/10.3389/fphar.2021.719631/full

Chronic Fatigue Syndrome Studies - 10/18/2023

 

A pilot study conducted at the University of Maryland Lyme Program evaluated the feasibility and impact of a multimodal integrative therapeutic intervention for patients with chronic symptoms attributed to a postinfectious syndrome. Participants attended two 1-hour individual instructional sessions, consisting of Ayurveda-based dietary intervention and breath-coordinated mind-body practice. Results showed that the intervention improved physical and mental health, fatigue, anxiety, and pain over a 12-month period. Employment status had significant effects on almost all outcome scores, and postinfectious state was associated with improvement in anxiety and PSS scores. The study concludes that a multimodal Ayurvedic and breath-coordinated mind-body therapeutic intervention is feasible and a potential nonpharmacologic therapeutic option for postinfectious syndrome patients.A Multimodal Ayurveda and Mind-Body Therapeutic Intervention for Chronic Symptoms Attributed to a Postinfectious Syndrome: A Pilot Study - PubMed (nih.gov)

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This review aims to educate healthcare professionals and the public about Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), a complex, chronic medical condition characterized by symptoms such as fatigue, malaise, cognitive dysfunction, immune dysfunction, sleep issues, pain, autonomic dysfunction, neuroendocrine and immune symptoms. ME/CFS is common, often disabling, and costly, with the Institute of Medicine (IOM) estimating between 836,000 and 2.5 million Americans affected annually. The disease is often misdiagnosed and treated, leading to patients suffering from unmet healthcare needs and food insecurity. The exact etiology of ME/CFS is unknown, but recent research is beginning to shed light on its causes, including infectious, genetic, immune, cognitive, metabolic, and biochemical abnormalities. Management involves supportive symptomatic treatment and strategic rest periods. Review of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: an evidence-based approach to diagnosis and management by clinicians - PubMed (nih.gov)

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The study compared flow-mediated dilation values between Long COVID, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), and healthy age-matched controls. Results showed significantly impaired endothelial function in both groups compared to healthy controls. Despite longer illness duration in ME/CFS, there was no difference in flow-mediated dilation between the two groups. The study suggests an increased cardiovascular risk in these populations, requiring careful monitoring and targeted interventions to improve endothelial function and mitigate long-term health implications. People With Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Exhibit Similarly Impaired Vascular Function - PubMed (nih.gov)

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The COVID-19 pandemic, caused by SARS-CoV-2, primarily causes acute respiratory infections but can lead to neurological complications and long-term sequela. Common symptoms include fatigue, myalgias, depression, anxiety, and cognitive and memory impairments. Even mild infections can cause neuroinflammation, impairing hippocampal neurogenesis and depleting oligodendrocytes. Strategies to restrain neuroinflammation, maintain better hippocampal neurogenesis, and preserve oligodendrocyte lineage differentiation may reduce the incidence of long-COVID. Role of Microglia, Decreased Neurogenesis and Oligodendrocyte Depletion in Long COVID-Mediated Brain Impairments - PubMed (nih.gov)   

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This study aims to demonstrate that oxygen consumption is a biomarker for Myalgic Encephalomyelitis (ME/CFS), a severe chronic disease. The researchers used two datasets: SF-36 responses from 2,347 confirmed records and a validation set of 239 cardiopulmonary exercise test results. The results showed a direct link between the Weber classification and the SF-36 questionnaire score. The 36-response matrix in the machine learning model was found to be more reliable than the subscale matrix for classifying patients with ME/CFS. The study suggests that low oxygen consumption on CPET can be considered a biomarker in ME/CFS patients. Unsupervised cluster analysis reveals distinct subtypes of ME/CFS patients based on peak oxygen consumption and SF-36 scores - PubMed (nih.gov)

How are Skin Diseases like Eczema Related to Chronic Fatigue Syndrome Caused by Dysbiosis in the Gut?

This is the best I could do for a picture of eczema. 

This is computer generated and does not usually look this bad.

Eczema is a common skin condition that causes inflammation, itching, and dryness of the skin. Chronic fatigue syndrome (CFS) is a complex disorder that causes persistent and unexplained fatigue, along with other symptoms such as pain, cognitive impairment, and sleep problems. Both eczema and CFS may be linked to an imbalance of the gut microbiome, which is the collection of bacteria, fungi, and other microorganisms that live in the digestive tract.

The gut microbiome influences many aspects of human health, including the immune system, metabolism, mood, and skin. When the gut microbiome is disrupted or imbalanced, it is called dysbiosis. Dysbiosis can happen due to various factors, such as diet, stress, medication use, infection, or genetics. Dysbiosis can cause inflammation, leaky gut syndrome (when the intestinal lining becomes more permeable and allows toxins and undigested food particles to enter the bloodstream), and altered immune responses.

Dysbiosis may play a role in the development and severity of eczema and CFS. Research suggests that people with eczema have lower diversity and higher levels of harmful bacteria in their gut microbiome compared to healthy individuals. These bacteria may trigger inflammation and allergic reactions in the skin, leading to eczema symptoms. Additionally, dysbiosis may affect the skin microbiome, which is the collection of microorganisms that live on the skin surface. An imbalance of the skin microbiome may allow harmful bacteria such as Staphylococcus aureus to colonize and infect the skin, worsening eczema.

Similarly, dysbiosis may contribute to CFS by causing inflammation, leaky gut syndrome, and immune dysfunction. These factors may result in systemic symptoms such as fatigue, pain, cognitive impairment, and sleep problems. Moreover, dysbiosis may affect the production of neurotransmitters such as serotonin and dopamine, which are involved in mood regulation and motivation. A lack of these neurotransmitters may cause depression and anxiety, which are common in people with CFS.

To improve gut health and potentially reduce eczema and CFS symptoms, some strategies include:

- Eating a balanced diet rich in fiber, fruits, vegetables, whole grains, legumes, nuts, seeds, healthy fats, and lean proteins. Avoiding processed foods, refined sugars, artificial sweeteners, alcohol, and foods that trigger allergies or sensitivities. A focus should also be paid for the consumption of NRF2 activators because NRF2 also plays a role in the health of the lining of the intestines and maintaining bacterial diversity. It also has been proposed as a possible treatment for atopic dermatitis (eczema) For more information on NRF2 see NRF2/NRF2 Activators (eirnnews.com) 

- Taking probiotics (live beneficial bacteria) or prebiotics (food for probiotics) supplements or eating fermented foods such as yogurt, kefir, sauerkraut, kimchi, miso, or kombucha. These may help restore the balance of the gut microbiome and support immune function.

- Managing stress levels by practicing relaxation techniques such as meditation, yoga, breathing exercises, or massage. Stress can negatively affect the gut microbiome and increase inflammation.

- Getting enough sleep by following a regular sleep schedule and avoiding caffeine, nicotine, alcohol, or screen time before bed. Sleep is essential for repairing the gut lining and regulating the immune system.

- Consulting a doctor before taking any medication that may affect the gut microbiome such as antibiotics or proton pump inhibitors. If necessary, taking these medications with probiotics or prebiotics to minimize their impact on the gut flora.

- Seeking medical advice if experiencing severe or persistent symptoms of eczema or CFS or signs of infection such as fever or pus.

References:

 Eczema and chronic fatigue can be caused by a condition called leaky gut. This condition arises when there is an imbalance of healthy bacteria to unhealthy bacteria in the intestines. On a cellular level this occurs when the lining of the gut becomes vaporous and toxins and undigested food particles then leak into the bloodstream. [Eczema and Chronic Fatigue Syndrome - The Optimum Health Clinic](https://www.theoptimumhealthclinic.com/2009/10/eczema-and-chronic-fatigue-syndrome/)

 Eczema is associated with lower bacterial diversity lower levels of beneficial species higher amounts of harmful bacteria species Staphylococcus aureus [Eczema](https://www.medicalnewstoday.com/articles/eczema-gut-health)

 The relationship between the gut microbiome and immunity is currently a major topic of research [The gut microbiome in skin disease | DermNet NZ](https://dermnetnz.org/topics/the-gut-microbiome-in-skin-disease)

 Certain triggers and stresses are thought to cause dysbiosis and cellular junction disruption allowing for increased intestinal permeability [Leaky Gut](https://nationaleczema.org/blog/leaky-gut/)

Researchers Realize that Macrophage Immune Cells in Inflammation in Fat Tissue Is Very Complex, Suggests New Study

 

According to a report on October 10, 2023 in "Obesity leads to a complex inflammatory response inside fat tissue" from ScienceDaily, despite its demonization, fat tissue is a highly intricate and vital organ. It plays a variety of roles in the body, including hormone production and energy storage. However, the obesity epidemic that has spread around the world because of modern lifestyles has also increased the prevalence of linked diseases like type 2 diabetes and cardiovascular disease.

To understand the relationship between obesity and poor health outcomes, researchers are trying to understand the fundamentals of fat tissue organization and, in particular, inflammation linked to obesity.

Using new technology researchers are learning more about inflammation biology that was not known before this study. Muir explained, "With adipose, it's a lot more challenging because the cell types are distributed evenly throughout the tissue, without defined cell layers." Adipocytes, or fat cells, proliferate and may eventually reach a limit that results in cell death and inflammation in cases of obesity.

Muir's team fed mice a "high-fat diet for 14 weeks, collected fat tissue, and used single cell and spatial analyses". This allowed them to gain a better understanding of the types of immune cells within adipose tissue and where they are in relation to each other in obesity.

During the study, researchers made an important discovery about the macrophage population in the samples. Macrophages are immune cells that clear away debris and dead cells. Unexpectedly, the researchers found the number of macrophages "that were highly different from each other and coming up at different times and becoming more dominant over time."

They distinguished between five categories, naming them Mac1, 2, 3, 4, and 5. Mac1 were found in the tissue of both fat and lean mice fed a typical diet. After eight weeks of the high-fat diet, "Mac2 and Mac3, which were recognized by their pro-inflammatory genes, reached their peak." After that, "pro-inflammatory Mac2 and Mac3 cells declined as the high-fat diet continued for 14 weeks, whereas Mac4 and Mac5 cells—which had minimal pro-inflammatory gene expression—predominated."

"In the field, the sort of macrophages that increase in obesity are thought to be stimulating inflammation. According to Muir, "Mac4 and Mac5 are the lipid associated macrophages (LAMs) that have been identified in previous study as well as by other scientists are the body’s attempt by the body to reduce a harmful degree of inflammation caused by pro-inflammatory macrophages and dying adipocytes." In addition, they were able to identify cells with a crown-like structure known to cause insulin resistance and tissue dysfunction that takes a long time to resolve. Further, they were able to identify the MACs and MAC5 (LAMs) genes that suggested the cell's attempt to limit the inflammatory response. (ScienceDaily)

Michigan Medicine - University of Michigan. "Obesity leads to a complex inflammatory response inside fat tissue." ScienceDaily. ScienceDaily, 10 October 2023. <www.sciencedaily.com/releases/2023/10/231010182936.htm>.

Cooper M. Stansbury, Gabrielle A. Dotson, Harrison Pugh, Alnawaz Rehemtulla, Indika Rajapakse, Lindsey A. Muir. A lipid-associated macrophage lineage rewires the spatial landscape of adipose tissue in early obesity. JCI Insight, 2023; 8 (19) DOI: 10.1172/jci.insight.171701

What are the Health Effects of too much Artificial Light Exposure at Night?

Artificial light at night (ALAN) is a common feature of modern urban life, but it can have negative consequences for human health and well-being. In contrast, natural light during the day is essential for maintaining a healthy circadian rhythm, which is the biological clock that regulates our sleep-wake cycle and other physiological functions.

The circadian rhythm is influenced by photoreceptors in the eye that are more sensitive to blue wavelengths of light, which are abundant in natural daylight. Exposure to natural light during the day helps to synchronize our internal clock with the external environment and promote alertness, mood, and cognitive performance. However, exposure to artificial light at night, especially blue light from LED sources, can disrupt this synchronization and suppress the production of melatonin, a hormone that induces sleep and has antioxidant and anti-inflammatory properties.

According to many studies, exposure to artificial light at night can increase the risk of various health problems, such as:

- Sleep disorders: Artificial light at night can interfere with the quality and quantity of sleep, leading to insomnia, daytime sleepiness, reduced memory and concentration, and impaired immune system.

- Depression: Artificial light at night can alter the levels of neurotransmitters such as serotonin and dopamine, which are involved in mood regulation. Lack of natural light during the day can also contribute to seasonal affective disorder (SAD), a type of depression that occurs in winter months.

- Obesity: Artificial light at night can affect the hormones that regulate appetite and metabolism, such as leptin and ghrelin. This can result in increased hunger, cravings, and calorie intake, as well as reduced energy expenditure and thermogenesis.

- Diabetes: Artificial light at night can impair glucose tolerance and insulin sensitivity, which are key factors in preventing type 2 diabetes. It can also disrupt the secretion of other hormones that regulate blood sugar levels, such as cortisol and growth hormone.

- Heart disease: Artificial light at night can increase blood pressure and heart rate, as well as inflammation and oxidative stress, which are linked to cardiovascular diseases such as hypertension, stroke, and heart attack.

- Cancer: Artificial light at night can suppress melatonin production, which has anti-cancer effects by modulating the immune system, DNA repair, and cell cycle. Several studies have found an association between exposure to artificial light at night and increased risk of breast cancer in women and prostate cancer in men.

To reduce the harmful effects of artificial light at night, it is recommended to:

- Avoid using electronic devices such as smartphones, tablets, computers, and TVs before bedtime or use blue-light blocking glasses or apps that filter out blue light.

- Use dimmer switches or low-wattage bulbs for indoor lighting at night and avoid bright or flashing lights.

- Use curtains or blinds to block out any outdoor lighting that may enter your bedroom window.

- Use red or amber lights for nightlights or alarm clocks, as they have less impact on melatonin production than white or blue lights.

- Expose yourself to natural light during the day, especially in the morning, to help reset your circadian rhythm and improve your mood and energy levels.

By following these tips, you can enjoy the benefits of artificial light without compromising your health and well-being.

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I recommend the use of light-blocking curtains in the bedroom. Learn more about black-out curtains

I also use an Echo Dot for an alarm and to ask Alexa verbally what the time is. I also use my Fitbit! 

NRF2 Research News for October 11, 2023

Osteoarthritis (OA) is an inflammatory joint disease causing progressive disability in the elderly. Reactive oxygen species (ROS) activate the NLRP3 inflammasome, leading to the secretion of proinflammatory IL-1β and IL-18. Nrf2, a transcription factor, regulates antioxidant enzyme expression. Researchers investigated the underlying mechanism of OA development by investigating NLRP3, ASC, Nrf2, and HO-1 expression in synovia and their regulatory networks. Results showed cartilage destruction and subchondral bone sclerosis in OA patients and OA model rats. The study found that ROS-induced oxidative stress may be the main cause of NLRP3 inflammasome activation and subsequent release of downstream factors during OA development. The discovery of a novel role of Nrf2/HO-1 signaling in NLRP3 production may facilitate the prevention and treatment of OA. Read more..,.Inhibition of Nrf2/HO-1 signaling leads to increased activation of the NLRP3 inflammasome in osteoarthritis - PubMed (nih.gov)

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Magnolol attenuates depressive-like behaviors by polarizing microglia towards the M2 phenotype through the regulation of Nrf2/HO-1/NLRP3 signaling pathway

Magnolol (MA) has been found to have an anti-depressant effect by inhibiting inflammation. However, its effect on microglia polarization in chronic unpredictable mild stress (CUMS)-induced depression remains unclear. A study conducted on mice and BV2 cells revealed that MA treatment relieved depressive behaviors, suppressed pro-inflammatory cytokines, promoted anti-inflammatory cytokines, and induced microglia-specific indicators. MA upregulated Nrf2 expression, reduced ROS concentration, promoted Nrf2 nucleus translocation, and prevented Nrf2 ubiquitination. The study concluded that MA attenuated CUMS-stimulated depression by inhibiting M1 polarization and inducing M2 polarization via Nrf2/HO-1/NLRP3 signaling. Magnolol attenuates depressive-like behaviors by polarizing microglia towards the M2 phenotype through the regulation of Nrf2/HO-1/NLRP3 signaling pathway - PubMed (nih.gov)

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Pharmacological Modulation of Nrf2/HO-1 Signaling Pathway as a Therapeutic Target of Parkinson's Disease

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta. Oxidative stress (OS) is a key contributor to PD, with genetic and environmental factors contributing to its pathogenesis. Nrf2, a transcription factor, activates protective genes like heme oxygenase-1 (HO-1), which protect cells from OS. Recent studies suggest that bioactive compounds can activate Nrf2/ARE and ameliorate PD-associated neurotoxin, suggesting pharmacological modulation of this signaling pathway as a potential therapeutic target. Pharmacological Modulation of Nrf2/HO-1 Signaling Pathway as a Therapeutic Target of Parkinson's Disease - PubMed (nih.gov)

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α-lipoic acid ameliorates hepatotoxicity induced by chronic ammonia toxicity in crucian carp (Carassius auratus gibelio) by alleviating oxidative stress, inflammation and inhibiting ERS pathway

High environment ammonia (HEA) threatens aquatic animals and human health. α-lipoic acid, an antioxidant, can mitigate oxidative stress and protect against chronic ammonia stress in crucian carp. Supplementation with α-lipoic acid induces humoral immunity, alleviates oxidative stress injury, and reduces liver injury induced by ammonia poisoning. α-lipoic acid ameliorates hepatotoxicity induced by chronic ammonia toxicity in crucian carp (Carassius auratus gibelio) by alleviating oxidative stress, inflammation and inhibiting ERS pathway - PubMed (nih.gov)

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Effects of epigallocatechin-3-gallate on oxidative stress, inflammation, and bone loss in a rat periodontitis model

The study investigates the effect of EGCG on oxidative and inflammatory stress and bone loss in experimental periodontitis. Results show that EGCG significantly reduces alveolar bone loss and inflammatory cells in rats, suggesting it inhibits these responses by modulating the Nrf2/HO-1/NLRP3/NF-κB p65 signaling pathway. Effects of epigallocatechin-3-gallate on oxidative stress, inflammation, and bone loss in a rat periodontitis model - PubMed (nih.gov)

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Targeting inflammasome pathway by polyphenols as a strategy for pancreatitis, gastrointestinal and liver diseases management: an updated review

Western lifestyle, characterized by unhealthy food consumption and decreased physical activity, is linked to obesity, pancreatitis, cardiovascular, gastrointestinal, and liver diseases. Polyphenols can modulate inflammasome-associated dysfunctions, restoring redox status. Targeting inflammasome pathway by polyphenols as a strategy for pancreatitis, gastrointestinal and liver diseases management: an updated review - PubMed (nih.gov)

The Nuts and Bolts of Applying for Disability

 

P38 Kinase/NRF2 Pathway May Play Important Role in Behaviors of Advancing Age and Parkinson's, Study Suggests

 

Researchers have made an important discovery in the biology of aging. According to a new study, scientists have found that a gene called P38 is responsible for determining lifespan and conditions related to aging. They found that flies that had an excess of p38 showed a delay in locomotor challenges that occur with aging. The flies that were engineered to lack P38 exhibited behaviors typical of advanced age, according to the report. Both processes involve oxidative stress. The flies lacking P38 showed elevated levels of oxidative stress while the flies that produce extra levels of p 38 exhibited minimal signs of oxidative stress.

Most of the researcher studies have focused on Parkinson's disease. Past studies have found that exposure to certain pesticides produce oxidative stress and can heighten the disease risk of Parkinson's in humans and animals. Vrailis-Mortimer wondered if antioxidants could prevent neuronal deterioration after exposure. What he found was that a cocktail of “superfoods” obtained from grocery store fruits, rich in antioxidants could recover the aging and mobility deficits in flies lacking p38. The cocktail consisted of five different fruits and the other cocktail contained acai berry. Supplementation of either “cocktail” extended their lifespan and increased their mobility almost like that of a normal fly. It also preserved their normal circadian rhythm.

Thus far, antioxidant supplements have demonstrated limited success in treating Parkinson's in experiments. However, Vrailis-Mortimer points out that in addition to dosing, timing may be a factor. She stated, “that most trials have been on patients in advanced stages of Parkinson's and that antioxidants may be less effective at later stages of disease.”

Note: 1) One pathway that p38 works through is the p38/MAPK/NRF2 pathway. Since other studies have demonstrated that antioxidants in berries and fruits are activators of the NRF2 pathway, it is likely that this pathway was activated by these “cocktails” although the determination of this was not a goal of the study. 2) “Mammalian p38 mitogen-activated protein kinases (MAPKs) are activated by a wide range of cellular stresses as well as in response to inflammatory cytokines.”

 

“Come Fly with Me”. Linus Pauling Institute. Digital Digest. Summer/Fall 2023. Pg. 7.

 Ana Cuenda and Simon Rousseau. p38 MAP-Kinases Pathway Regulation, Function and Role in Human Diseases, Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. Volume 1773, Issue 8, 2007. Pages 1358-1375,

 

Cherries Offer Numerous Health Benefits and May Reduce Exhausting Effects of Exercise

I would suggest anyone that suffers from any of the environmental conditions to think about adding cherry juice to their daily dietary routine. Even though some researchers are still unconvinced that tart cherry juice is as nutritious as many health experts believe, there have been several studies over the last 10 years that has provided evidence there are beneficial health effects especially after exercise. Two past studies suggest that cherry juice may offer anti-inflammatory effects from other biological pathways than just from antioxidant-producing pathways. In one study, arthritis patients who consumed tart juice for six weeks had a 23% reduction in c-reactive protein. Another study showed that consumption of cherry juice showed an increased expression of antioxidant genes and proteins after seven days that can reduce oxidative stress. The study also showed enhanced recovery from exercise-induced muscle damage. (McHugh)

In a new study from New Zealand, a new study provided more information on the nutritious value of cherries. Even though it is important to point out that every cultivar of cherries have their own chemical properties, but this study can at least provide some background on the nutrients and compounds that are contained in the cherries tested. (Also, there are more cherries in juice than can be eaten to get the antioxidants levels studied during past experiments.) During this study, six species of cherries was studied including Bing, Rainier, Kordia, Lapins, Sweetheart and Staccato. Dr Rashidinejad, the lead researcher, explained "We concluded that all six varieties were rich sources of different nutrients: minerals, vitamins, amino acids and phenolic compounds – the antioxidants. These latter compounds, the phenolic compounds, were what most interested us because they are potent antioxidants with numerous scientifically proven health-promoting properties. The study results found numerous nutrients in the fresh, frozen and packaged samples. Just some of the vitamins they found in healthy amounts were vitamins A, C and B vitamins and about 30 phenolic antioxidative compounds. The good news is they found little differences in the method of processing on the preservation of nutritional value. 

To read the full article on the study from New Zealand, click here.

McHugh MP. "Precovery" versus recovery: Understanding the role of cherry juice in exercise recovery. Scand J Med Sci Sports. 2022 Jun;32(6):940-950. doi: 10.1111/sms.14141. Epub 2022 Feb 14. PMID: 35119142; PMCID: PMC9306613.

What are Postbiotics and Why We May Need to Consume Them

Postbiotics are dead or nonliving bacteria that offer health benefits when taken. They can be byproducts or metabolites produced by probiotics during their active phase, such as probiotics fermenting dietary fiber, which produce short-chain fatty acids like butyrate or acetate. These postbiotics can help with increased immunity, reduced digestive symptoms, and potentially help people with food allergies. However, research on postbiotics is challenging due to a lack of a standard definition.

"Postbiotics are not found in food, but consumption of pre-biotic and probiotic-rich food will lead to increased postbiotic production and provide other nutrients like vitamins, minerals, and fiber." Prebiotics can be found in foods like oats, beans, apples, bananas, and onions. Prebiotics can be found in foods like oats, beans, apples, bananas, and onions, while probiotics in fermented foods like yogurt, sauerkraut, tempeh, miso, kefir, and kimchi.

Postbiotic supplements may not be suitable for everyone, including those with digestive disorders, discomfort, pregnancy, or certain chronic conditions. They are not regulated by the FDA and not all supplements contain the amounts they claim, especially if they haven't been third-party-tested. If someone's diet is lacking in prebiotic and probiotic foods, talking to a medical professional about a third-party tested supplement may be an option to get some of these health benefits.

For postbiotic supplements, it is recommended to consult a medical doctor before taking any gut health supplement. Read full article: What Are Postbiotics? | Food Network Healthy Eats: Recipes, Ideas, and Food News | Food Network

Recent Studies on Long Covid

 

A study comparing COVID-19 patients to pre-pandemic subjects found that COVID-19 survivors had lower levels of fT3 and fT4, higher TSH and aTPO antibodies, and higher levels of prolactin and testosterone. However, no significant differences were found in body composition or metabolic and glycemic parameters between cases and controls. The study suggests that SARS-CoV-2 infection may have long-term consequences on the endocrine system, including suppressed thyroid gland function, prolactin, and male sex hormone secretion. However, COVID-19 had no significant impact on glycemic parameters, lipid profiles, liver function, body composition, cortisol levels, and estradiol levels. Long-term effects of COVID-19 on the endocrine system - a pilot case-control study - PubMed (nih.gov)    

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A study examining the natural history, symptomology, and risk profile of long-term post-acute SARS-CoV-2 fatigue in US patients found that those with severe fatigue were younger, female, had more anxiety and depression, had a higher resting heart rate, reported more sick days, and were less physically active post-COVID. They were more likely to have a diagnosis of chronic kidney disease but less likely to have a history of cancer. Fatigue was significantly correlated with impairment of all PROs administered after COVID-19 infection. Severe, Persistent, Disruptive Fatigue Post-SARS-CoV-2 Disproportionately Affects Young Women - PubMed (nih.gov)  

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A study involving 113 UK Armed Forces participants found that COVID-19 infection can lead to a prolonged syndrome including fatigue, exercise intolerance, mood, and cognitive problems. The study found that at 5 and 12 months, exposed participants had higher PHQ-9, PCL-5, and FAS scores than controls. However, by 18 months, GAD-7 was not significantly different to controls. The study also found that exposed participants recorded significantly lower distances on the 6-minute walk test. The study concluded that COVID-19 exposure improved cognitive performance and depression up to 12 months. How long is Long-COVID? Symptomatic improvement between 12 and 18 months in a prospective cohort study - PubMed (nih.gov)

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A study by CO-FLOW aimed to evaluate the long-term consequences of COVID-19 on return to work and health-related quality of life (HRQoL) in adult patients up to one year after hospitalization. The study involved 371 participants and collected data at 3, 6, and 12 months post-discharge. Results showed that 50% of participants had not returned to work, and 15% only partially returned. Factors such as ICU admission, persistent fatigue, female sex, and older age were independently associated with no return to work. The study concluded that only 69% of patients fully returned to work one year after hospitalization, with 15% not returning and 16% partially returning. Return to work and health-related quality of life up to 1 year in patients hospitalized for COVID-19: the CO-FLOW study - PubMed (nih.gov)

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Research indicates that SARS-CoV-2 infection may cause gut dysbiosis, affecting the gut-lung axis and reducing antimicrobial peptide production. Studies show a decline in alpha diversity and increased dissimilarity in beta diversity of gut microbiota during COVID-19, leading to heightened inflammation in patients. This is linked to the severity of the disease and post-acute COVID-19 syndrome. Certain gut microbiota species could aid in diagnosis, prediction, and treatment of severe cases. Profiles of gut microbiota associated with clinical outcomes in patients with different stages of SARS-CoV-2 infection - PubMed (nih.gov)

ME/CFS Research Roadmap : Nervous System

 

This is informative but technical.

What is Hormesis and What Does it have to do with Polyphenols?

Hormesis is a biological phenomenon that describes how low doses of a substance, or a stressor can have beneficial effects, while high doses can have harmful effects. Hormesis is often represented by a U-shaped or J-shaped curve, where the optimal dose is somewhere in the middle.

Polyphenols are a large group of natural compounds that are found in plants, fruits, vegetables, tea, wine, and other foods. Polyphenols have antioxidant, anti-inflammatory, and neuroprotective properties, and they can modulate various cellular pathways and gene expressions.

Polyphenols are considered to be hormetic dietary phytochemicals, meaning that they can activate adaptive cellular stress response pathways that enhance the health and function of the organism. However, polyphenols can also have negative consequences at high doses, such as generating reactive metabolites, interfering with detoxification enzymes, or inducing oxidative stress.

Therefore, the dose and the context are very important factors to consider when evaluating the effects of polyphenols on health and disease. Some of the factors that can influence the hormetic response of polyphenols include:

- The type and source of polyphenols

- The bioavailability and metabolism of polyphenols

- The individual variability and genetic background of the organism

- The duration and frequency of exposure to polyphenols

- The interaction with other dietary components or drugs

- The presence of other stressors or diseases

Some examples of how polyphenols can exert hormetic effects on different systems and conditions are:

- Polyphenols can improve cognitive function and prevent neurodegenerative diseases by modulating synaptic plasticity, neurogenesis, neuroinflammation, and oxidative stress. However, excessive intake of polyphenols can impair cognitive function by disrupting neurotransmission, neuronal excitability, and mitochondrial function.

- Polyphenols can protect against cardiovascular diseases by improving endothelial function, reducing blood pressure, inhibiting platelet aggregation, and lowering cholesterol levels. However, high doses of polyphenols can have pro-oxidant and pro-inflammatory effects that can damage the vascular system.

- Polyphenols can prevent cancer by inducing apoptosis, inhibiting angiogenesis, modulating epigenetic mechanisms, and modulating immune responses. However, high doses of polyphenols can also promote carcinogenesis by inducing DNA damage, enhancing mutagenesis, or stimulating tumor growth.

In conclusion, hormesis is a concept that can help us understand the complex and dynamic effects of polyphenols on health and disease. By finding the optimal dose and context for each individual and condition, we can harness the beneficial effects of polyphenols while avoiding their potential risks.

Recent News About MCS and MCAD!

Mast cells (MCs) are abundant in areas exposed to pathogens and are activated through pathogen recognition or interaction with other immune cells. They release pre-stored mediators, enhancing pathogen clearance. MCs are protective against parasites and can respond to viral, bacterial, and fungal infections. Vitamin D, a fat-soluble hormone, regulates calcium and phosphorus metabolism and has immunomodulatory properties. A vitamin D deficiency can activate MCs, focusing on its role in MC stabilization. https://pubmed.ncbi.nlm.nih.gov/37759494/ #MCS #MCAS #MCAD

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Mast Cell Activation Syndrome (MCAS) is a recently recognized, multisystem disorder with a high prevalence. It is closely linked to gastric dysmotility, dysautonomia, joint hypermobility disorders, and autoimmunity. A 42-year-old female with chronic SIBO presented to a clinic for treatment. She was found to have other conditions, including a mast cell-mediated disorder and joint hypermobility. Treatment improved with ketotifen and remission of SIBO with low-dose naltrexone. https://pubmed.ncbi.nlm.nih.gov/37752934/ #MCS #MCAD #MCAS

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What are the Health Benefits of the Mediterranean Diet, the DASH Diet, and the MIND Diet? What are the Differences Between Them?

 If you are looking for a healthy diet that can improve your brain function and prevent dementia, you may have heard of the Mediterranean, DASH and MIND diets. These are three popular diets that have been shown to benefit your heart and brain health. But what are the benefits and what are the differences between them?

The Mediterranean diet is based on the traditional eating patterns of people living in countries bordering the Mediterranean Sea, such as Greece, Italy and Spain. It emphasizes eating plenty of fruits, vegetables, whole grains, legumes, nuts, seeds, olive oil, fish and seafood, moderate amounts of dairy products, eggs and poultry, and occasional red meat and wine. The Mediterranean diet has been linked to lower risks of heart disease, diabetes, cancer and cognitive decline ( 1 ).

The DASH diet stands for Dietary Approaches to Stop Hypertension. It was designed to lower blood pressure and prevent cardiovascular diseases. It is similar to the Mediterranean diet in that it also encourages eating fruits, vegetables, whole grains, low-fat dairy products, lean meats, fish, poultry, nuts and seeds. However, it limits salt intake to less than 2,300 mg per day (or 1,500 mg for people with high blood pressure) and restricts sweets, sugary drinks and red meat more than the Mediterranean diet ( 2 ).

The MIND diet is a combination of the Mediterranean and DASH diets that focuses specifically on brain health. It stands for Mediterranean-DASH Intervention for Neurodegenerative Delay. It recommends eating 10 brain-healthy foods and avoiding 5 unhealthy foods. The 10 foods are green leafy vegetables, other vegetables, berries, nuts, olive oil, whole grains, fish, beans, poultry and wine. The 5 foods to avoid are butter and margarine, cheese, red meat, fried food and pastries and sweets. The MIND diet has been shown to reduce the risk of Alzheimer's disease by up to 53% and slow down cognitive aging by 7.5 years ( 3 ).

The main differences between the three diets are the amount and type of foods they recommend. For example, the MIND diet emphasizes eating berries (especially blueberries and strawberries) and green leafy vegetables (such as spinach and kale) more than the other two diets because they have shown compelling evidence for protecting the brain from oxidative stress and inflammation ( 4 , 5 ). The MIND diet also allows wine in moderation (one glass per day) because it may have beneficial effects on brain function ( 6 ). On the other hand, the DASH diet is more restrictive in salt intake than the other two diets because it aims to lower blood pressure.

All three diets are healthy choices for your overall well-being. They share some common principles such as eating more plant-based foods, choosing healthy fats over saturated fats, limiting processed foods, added sugars, and enjoying your food in moderation. You can choose the one that suits your preferences, goals and lifestyle best. Or you can mix and match elements from each diet to create your own personalized plan.

Sources:

1. https://www.healthline.com/nutrition/mediterranean-diet-meal-plan

2. https://www.healthline.com/nutrition/dash-diet

3. https://www.healthline.com/nutrition/mind-diet

4. https://blog.invitehealth.com/mind-diet-combining-mediterranean-dash/

5. https://brain.health/blog/articles/mediterranean-dash-and-mind-diets-a-beginners-guide/

6. https://www.alzheimers.org.uk/get-support/healthy-living/alcohol-and-dementia