Posted on Osteoporosis, Rheumatoid arthritis

Two key genes identified linking rheumatoid arthritis and osteoporosis

Two key genes, ATXN2L and MMP14, that are most strongly linked to both diseases

Of the many genes involved in rheumatoid arthritis and osteoporosis, the researchers identified two essential genes, ATXN2L and MMP14, most strongly linked to both diseases—credit Lo et al.

Rheumatoid arthritis is a prevalent condition that affects approximately 17 million people globally. This disease occurs when the immune system mistakenly attacks the joints, leading to pain, swelling, and damage to the cartilage and bones. Additionally, individuals with rheumatoid arthritis are at an increased risk of developing osteoporosis, a more serious condition that can arise from the bone damage caused by the immune response as well as from certain medications used to treat the disease.

In the journal APL Bioengineering from AIP Publishing, researchers from Da-Chien General Hospital, China Medical University, and Chang Gung University used analytical tools and machine learning algorithms to identify two genes associated with rheumatoid arthritis and osteoporosis. These genes could serve as diagnostic tools and potential targets for treatment.

Both diseases revolve around a key mechanism that helps regulate the body’s functions. Apoptosis, or programmed cell death, is an essential process that immune cells use to eliminate malfunctioning or unnecessary cells. However, malfunctions in this process can cause immune cells to mistakenly target random cells, often resulting in severe consequences.

“Excessive apoptosis of bone-forming cells in rheumatoid arthritis leads to joint destruction and inflammation,” stated author Hao-Ju Lo. “This same process also results in weakened bones in osteoporosis, highlighting the necessity of managing both conditions concurrently.”

Because of its central role, the researchers set out to find genes involved with apoptosis that were closely linked to both diseases. Drawing from an extensive database of genetic information, they gathered dozens of sequenced genomes from people with rheumatoid arthritis and osteoporosis to look for similarities. Combing through this mountain of genetic data was no easy task, so they turned to recently developed computational methods to narrow their search.

“We used bioinformatics tools to analyze large gene datasets, focusing on genes active in rheumatoid arthritis and osteoporosis,” said Lo. “We applied machine learning techniques, such as Lasso and Random Forest, to refine our search, identifying two key genes — ATXN2L and MMP14 — that play significant roles in both diseases.”

According to their analysis, these two genes are significantly associated with the progression of rheumatoid arthritis and osteoporosis. ATXN2L regulates processes like apoptosis, so malfunctions in this gene are likely to trigger both rheumatoid arthritis and osteoporosis. MMP14 contributes to building extracellular tissue like cartilage and could be responsible for the breakdown of joint tissue that leads to rheumatoid arthritis.

“Our analysis revealed that these genes are involved in immune regulation and bone metabolism, suggesting they could be useful markers for diagnosing or treating rheumatoid arthritis and osteoporosis,” said Lo.

With two potential targets identified, the authors plan to use these results as a starting point to develop new treatment options for patients suffering from these two linked diseases.

“We plan to validate these findings with experimental studies and explore how targeting these genes could improve treatment outcomes,” said Lo. “Our future research may also involve developing personalized therapies, leveraging AI and machine learning to predict which patients are most at risk for osteoporosis.”

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Posted on Multiple Sclerosis, Pain Management

Eleven Ways Multiple Sclerosis Causes Pain

Can multiple sclerosis cause pain? Yes, it can! This video highlights 11 common pain syndromes associated with MS, including trigeminal neuralgia, the “MS hug,” neuropathic pain, muscle spasms, and several others.

Posted on Cognitive dysfunction, Diabetes, Diet

Blood sugar control is a big factor in slowing brain aging! What about the Mediterranean diet?

The Green Mediterranean Diet Shows Promise
The Green Mediterranean Diet Shows Promise

Age-related brain atrophy refers to the gradual loss of neurons and shrinkage of brain tissue, which is a natural part of the ageing process. This condition can contribute to cognitive decline and various neurological issues. While ageing itself cannot be prevented, recent research from an 18-month dietary intervention provides hope that lifestyle and dietary changes may help slow down brain ageing.

Brain age, determined through MRI measurements of the hippocampus and lateral ventricles, reflects the biological aging of the brain, which may differ from a person’s chronological age. Chronological age is simply the number of years a person has lived, while brain age indicates the actual health of the brain. Generally, as we age, the hippocampus tends to shrink, and the lateral ventricles tend to expand, which serve as indicators of brain ageing. Some individuals may have a brain age that is younger or older than their chronological age. A younger brain age suggests better cognitive health, whereas an older brain age may indicate accelerated ageing and an increased risk of cognitive decline.

The study found that a decline in HbA1c and key markers of long-term blood sugar levels is associated with significant positive changes in specific brain regions commonly affected by age-related atrophy. It suggests that improved blood sugar control could be one of the most important factors in slowing down age-related brain changes.

Previous research has shown the benefits of the Green Mediterranean (Green-Med) diet, particularly its positive effects on blood sugar control. This diet is rich in polyphenols from plant-based sources such as Mankai—a high-protein aquatic plant—and green tea, while being low in red and processed meats. The current study reinforces these findings, suggesting that the Green-Med diet not only supports metabolic health but may also have protective effects on brain structure and function.

Posted on autoimmune conditions, Diet, Multiple Sclerosis

How the keto diet could one day treat autoimmune conditions

Keto and paleo diets were found to be the least sustainable -- and have the lowest diet quality scores -- of the six popular diets examined

Researchers have long believed that the keto diet could help reduce an overactive immune system and benefit individuals with conditions such as multiple sclerosis.

Now, they have reason to believe it could be true.

Scientists at UC San Francisco have discovered that the diet makes the gut and its microbes produce two factors that attenuated symptoms of MS in mice.

If the study translates to humans, it points toward a new way of treating MS and other autoimmune disorders with supplements.

The keto diet severely restricts carbohydrate-rich foods like bread, pasta, fruit and sugar but allows unlimited fat consumption.

Without carbohydrates to use as fuel, the body breaks down fat instead, producing compounds called ketone bodies. Ketone bodies provide energy for cells to burn and can change the immune system.

Working with a mouse model of MS, the researchers found that mice who produced more of a particular ketone body, called β-hydroxybutyrate (βHB), had less severe disease.

The additional βHB also prompted the gut bacterium Lactobacillus murinus to produce an indole lactic acid (ILA) metabolite. This blocked the activation of T helper 17 immune cells involved in MS and other autoimmune disorders.

“What was exciting was discovering that we could protect these mice from inflammatory diseases simply by putting them on a diet supplemented with these compounds,” said Peter Turnbaugh, PhD, of the Benioff Center for Microbiome Medicine.

Earlier, Turnbaugh had shown that when secreted by the gut, βHB counteracts immune activation. This prompted a postdoctoral scholar working in his lab, Margaret Alexander, PhD, to see if the compound could ease the symptoms of MS in mice.

In the new study, which appears Nov. 4 in Cell Reports, the team examined how the ketone body-rich diet affected mice unable to produce βHB in their intestines and found that their inflammation was more severe.

However, when the researchers supplemented their diets with βHB, the mice got better.

To find out how βHB affects the gut microbiome, the team isolated bacteria from the guts of three mice fed either the keto diet, a high-fat diet, or the βHB supplemented high-fat diet.

Then, they screened the metabolic products of each group’s distinct microbes in an immune assay and determined that the diet’s positive effects were coming from a member of the Lactobacillus genus: L. murinus.

Two other techniques, genome sequencing and mass spectrometry, confirmed that the L. murinus they found produced indole lactic acid, which is known to affect the immune system.

Finally, the researchers treated the MS mice with either ILA or L. murinus, improving their symptoms.

Turnbaugh cautioned that the supplement approach still needs to be tested in people with autoimmune disorders.

“The big question now is how much of this will translate into actual patients,” he said. “But I think these results provide hope for the development of a more tolerable alternative to helping those people than asking them to stick to a challenging restrictive diet.”