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Weight loss is encouraged by a naturally occurring molecule that suppresses appetite.

Weight loss is encouraged by a naturally occurring molecule that suppresses appetite.

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Researchers from Stanford Medicine have discovered a naturally occurring molecule that functions similarly to semaglutide, commonly marketed as Ozempic, in terms of appetite suppression and weight loss. Interestingly, studies conducted on animals also revealed that it was effective without some of the negative effects of the medication, including nausea, constipation, and a marked loss of muscle mass.

The recently identified molecule, BRP, appears to provide a more focused method of body weight loss by activating distinct neurons in the brain and acting through a different but comparable metabolic pathway. In addition to the brain, semaglutide also targets receptors in the pancreas, gut, and other tissues. Because of this, Ozempic has a variety of effects, such as lowering blood sugar levels and slowing the passage of food through the digestive system. BRP, on the other hand, seems to have a specific effect on the hypothalamus, which regulates metabolism and appetite.

Without using artificial intelligence to sort through dozens of proteins in a class known as prohormones, the study would not have been feasible. Prohormones are physiologically inert molecules that become active when other proteins break them down into smaller molecules known as peptides. Some of these peptides then act as hormones to control intricate biological processes in the brain and other organs, such as energy metabolism.

Numerous functional peptide progeny can be produced by splitting each prohormone in different ways. However, it is challenging to separate peptide hormones which are comparatively uncommon from the biological soup of the far more common natural byproducts of protein processing and degradation using conventional protein isolation techniques. The prohormone convertase 1/3, which is known to play a role in human obesity, was the focus of the study. It separates prohormones at particular amino acid sequences. Glucagon-like peptide 1, or GLP-1, is one of the peptide products that control blood sugar and appetite; semaglutide functions by simulating GLP-1’s physiological effects. To find additional peptides involved in energy metabolism, the team looked to artificial intelligence.

Peptide predictor
The researchers created a computer algorithm they called Peptide Predictor to find common prohormone convertase cleavage sites in all 20,000 human protein-coding genes, eliminating the need to manually separate proteins and peptides from tissues and use methods like mass spectrometry to identify hundreds of thousands of peptides. They then concentrate on genes that encode proteins with four or more potential cleavage sites and that are secreted outside of the cell, which is a crucial feature of hormones. By doing this, the search was reduced to 373 prohormones, which is a manageable quantity to check for biological effects.

Prohormone convertase 1/3 was expected to produce 2,683 distinct peptides from the 373 proteins, according to Peptide Predictor. Coassolo and Svensson concentrated on sequences that the brain is probably biologically active. They tested 100 peptides, including GLP-1, for their capacity to stimulate neuronal cells cultured in a lab. The GLP-1 peptide, as anticipated, had a strong effect on the neurons, causing them to become three times more active than the control cells. However, a tiny peptide consisting of only 12 amino acids increased the cells’ activity ten times more than controls. Based on its parent prohormone, BPM/retinoic acid inducible neural specific 2, also known as BRINP2 (BRINP2-related-peptide), the researchers called this peptide BRP.

An intramuscular injection of BRP before feeding decreased food intake over the following hour by up to 50% in both animal models, according to the researchers’ testing of the drug’s effects on lean mice and minipigs, which more closely resemble human metabolism and eating patterns than mice do. Over 14 days, obese mice given daily injections of BRP lost an average of 3 grams, almost entirely as a result of fat loss, whereas control mice gained roughly 3 grams. Additionally, the mice showed enhanced insulin and glucose tolerance.

Behavioral studies of the pigs and mice revealed no differences in the fecal production, water intake, anxiety-like behavior, or movement of the treated animals. Additionally, additional research on brain and physiological activity revealed that BRP activates metabolic and neuronal pathways independently of those triggered by semaglutide or GLP-1. In addition to further deconstructing the mechanisms of action of BRP, the researchers aim to identify the cell-surface receptors that bind it. If the peptide is successful in controlling human body weight, they are also looking into ways to prolong its effects on the body so that a more convenient dosing schedule can be used.

According to Svensson, the dearth of efficient medications to treat obesity in people has existed for many years. The ability of semaglutide to reduce appetite and body weight is superior to anything we have tested previously. We are very interested in finding out if it works and is safe for people. The study included contributions from researchers at the University of British Columbia, the University of Minnesota, and the University of California, Berkeley.

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What Does Inflammation Do to the Body?

What Does Inflammation Do to the Body?

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The body’s immune system reacts to perceived injury or infection by producing inflammation. Because a lot of white blood cells are rushing into the injured area to fight infection and promote healing, inflammation makes the area red and swollen. Infection and inflammation are not the same thing, and it’s critical to distinguish between the two. The invasion of disease-causing organisms into body tissues, their subsequent growth, and the immune system’s response to the organisms and the toxins they produce are all considered infections. This indicates that although an infection is usually linked to inflammation, an infection is not always present when an inflammatory response occurs.

The body’s defense mechanism
The immune system uses inflammatory cells and cytokines during an injury or infection, which in turn triggers the production of more inflammatory cells. This triggers the body’s inflammatory response, which the cells use to ensnare pathogens or toxins and begin the healing process of the damaged tissue. Pain, heat, redness, swelling, and loss of function are all indicators of inflammation. 4 Loss of function can include breathing difficulties if you have bronchitis (inflammation of the bronchi), losing the ability to smell during a cold, or being unable to move an inflamed joint properly. All five of these symptoms, however, are not always the result of an inflammatory response; some forms of inflammation can manifest silently and without any symptoms.

In response to an inflammatory response, the immune system may also release inflammatory mediators from different immune cells, including hormones like histamine and bradykinin. Inflamed areas can turn red and feel hot because these hormones cause vasodilation, which widens the tissue’s tiny blood vessels and increases blood flow to the injured area. More blood flow also makes it possible for more immune cells to move to the site of the injury and promote healing.

Acute inflammation: A short-term response
Short-term acute inflammation and long-term chronic inflammation are the two primary forms of inflammation. The immune system’s quick and transient reaction to an unexpected injury or disease is known as acute inflammation. Inflammatory cells make up this transient reaction, which travels to the site of an infection or injury to initiate the healing process. The duration of this kind of inflammation can range from a few hours to several days. Acute inflammation is frequently brought on by wounds like cuts, bacterial infections like step throat, and viral infections like the flu that can irritate the throat.

Enteritis, or inflammation of the small intestine, can also be brought on by other kinds of bacterial and viral infections. This type of inflammatory response can aid in the healing process because fever can show that the immune system is healthy, which is very active and energy-demanding. This is because a fever may increase metabolism, which allows for the production of more antibodies and immune cells to aid in the fight against infection.

Nonetheless, it is critical to be mindful of immune system complications, such as septicemia, also referred to as blood poisoning, which is an uncommon but serious infection-related complication. Feeling very sick, having a high fever, and chills are some of the symptoms of this complication. If the bacteria that has entered the body multiply rapidly in one area of the body and then a significant number of them abruptly enter the bloodstream, septicemia may result. This could happen for many reasons, including the body’s inability to combat the infection locally, a compromised immune system, or an extremely aggressive bacterium.

Chronic inflammation: A silent threat
Although inflammation is a helpful immune response, the body does not always benefit from it. In certain diseases, the immune system unintentionally fights against the body’s cells, which can lead to dangerous illnesses. Even in the absence of danger, the body still releases inflammatory cells when there is chronic inflammation. There may be times when symptoms get better and times when they get worse over months or even years of chronic inflammation. Examples include inflammatory bowel disorders like Crohn’s disease or ulcerative colitis, a chronic skin condition called psoriasis, and rheumatoid arthritis, which is characterized by persistent joint inflammation.

Numerous inflammatory diseases, including cardiovascular conditions like heart disease, autoimmune diseases like lupus, and even some types of cancer, have been connected by researchers to chronic inflammation. Acute inflammation is typically brought on by injuries and infections, but environmental factors like daily life activities and exposure to toxins are usually the primary cause of chronic inflammation. Low levels of physical activity, long-term stress, having a high body mass index (BMI) or excess weight around the stomach, eating inflammatory foods, sleep disturbances, exposure to toxins, and an imbalance of good and bad gut bacteria are all common causes of chronic inflammation.

The ripple effect: Inflammation and disease
Numerous body systems, including the cardiovascular system, can be significantly impacted by inflammation, as cardiovascular diseases like atherosclerosis are the world’s leading cause of death. Inflammatory mediators play a significant role in atherosclerosis, helping to recruit cells initially for the development of plaques in blood vessels and ultimately leading to vessel rupture. Inflammation is one way that cardiac stress shows up in the body, with impacted cardiac tissues exhibiting elevated levels of inflammatory cytokines and chemokines.

The most frequent cause of heart attacks is coronary atherosclerosis, which causes the heart’s tissue to deteriorate. As the cardiac cells die during a heart attack, inflammatory cells migrate to the necrotic tissue site to remove debris and dead cells. Moreover, polygenic inflammatory bowel disease, which includes Crohn’s and ulcerative colitis, can result from excessive inflammatory reactions to gut microbial flora. These two digestive disorders are driven by cytokines, which can also result from non-infectious intestinal inflammation.

It’s interesting to note that elevated inflammation has also been linked to depression and exhaustion, with alterations observed in the central nervous system (CNS). Increased blood-brain barrier permeability brought on by inflammation can make it simpler for immune cells or inflammatory molecules to enter the central nervous system. People who suffer from depression and exhaustion may experience structural and functional changes as a result of inflammatory signaling in the central nervous system.

As was already mentioned, inflammation plays a major role in chronic illnesses, including autoimmune conditions like rheumatoid arthritis. Additionally, there is mounting evidence that inflammation plays a significant role in the development and course of diabetes. Since CRP and other indicators of active inflammation are linked to an increased risk of diabetes in people with rheumatoid arthritis, systemic inflammation associated with the disease may also raise the chance of developing diabetes in the future.

Reducing inflammation: Lifestyle and medical approaches
Lowering inflammation is essential for lowering the risk of diseases linked to inflammation. This can involve eating an anti-inflammatory diet, as many foods, including leafy greens, fresh fruits, and fatty fish like salmon, can help reduce inflammation in the body. 2 To lower and prevent inflammation in the body, some dieticians advise following the DASH or Mediterranean diets, which increase potassium and decrease sodium intake.

Frequent exercise can reduce chronic stress and stress-triggered hormones, as well as the risk for chronic inflammation. This includes 150 minutes per week of moderate-intensity exercise, such as walking. Yoga, deep breathing, mindfulness, and other relaxation techniques that soothe the nervous system are examples of stress management strategies. Furthermore, supplements like zinc and omega-3 that may lower inflammation and promote the body’s ability to repair itself may be included in over-the-counter anti-inflammatory drugs. In addition to ibuprofen, aspirin, or naproxen, nonsteroidal anti-inflammatory drugs (NSAIDs) are also available over-the-counter and can be used to reduce inflammation.

A corticosteroid injection may also be administered by a medical professional to reduce inflammation in particular muscles or joints. Prednisone can also be prescribed by medical professionals to treat inflammatory diseases like vasculitis, lupus, and arthritis. In order to prevent inflammation-related disorders and diseases, it is important to reduce chronic inflammation on a daily basis through exercise, a healthy diet, stress reduction, and maintaining a healthy weight.

A comprehensive anti-aging approach may lessen neurodegeneration.

A comprehensive anti-aging approach may lessen neurodegeneration.

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Recognizing the connection between neurodegenerative diseases and aging: research, risks, and new treatments. The rate at which the world’s population is aging is unprecedented. One billion people are 60 years of age or older today, and by 2050, that number is predicted to double. One of the main causes of neurodegenerative diseases (NDDs) and their related conditions, such as vascular disease, is aging.

After the ages of 60 to 65, there is a significant increase in the risk of developing NDDs, including Parkinson’s disease (PD) and Alzheimer’s disease (AD). The prevalence of AD increases from 5% among those 65 to 74 to 13% in the next ten years and 33% after the age of 85. Dementia affects 55 million people today, and by 2030, that figure is expected to rise to 78 million. The second most common cause of disability-adjusted life years (DALYs), which include years of life lost (YLLs) and years lived with disability (YLDs), is dementia. Between 60 and 80 percent of these cases are caused by AD.

In addition to the psychological and physical strain of caring for people with NDDs, there will likely be a significant increase in the financial burden. Between 2015 and 2050, the cost of dementia care alone is expected to tenfold increase, reaching $91 trillion. Since there is currently no cure for NDDs, research is being done to create treatments that can improve physical and cognitive function or at the very least slow the disease’s progression.

Aging and Neurodegenerative Diseases
Using a complex adaptive system (CAS) model often referred to as a “network of networks” a recent study published in Signal Transduction and Targeted Therapy investigates the role of aging in NDDs. According to this model, the brain serves as the center of a networked system, and aging-related disruptions cause homeostasis to deteriorate and NDDs to ineffective DNA repair, accumulated genetic mutations, protein accumulation, compromised nutrient sensing, oxidative stress, epigenetic modifications, chronic inflammation (inflammation), stem cell exhaustion, and mitochondrial dysfunction are some of the biological changes brought on by aging that lead to NDDs.

Other aging-related factors in the brain include aberrant neural circuit activity and excessive activation of immune cells (glia). Amyloid-beta (Aβ), hyperphosphorylated tau, and α-synuclein (α-syn) are among the harmful proteins that build up as a result of neuronal mutations and epigenetic modifications.

These proteins worsen mitochondrial dysfunction, increase oxidative stress, and cause neuroinflammation, all of which further harm neurons. These harmful proteins are difficult for senescent glial cells to eliminate, which leads to persistent inflammation. A cycle of inflammation and neuronal damage is produced when dangerous substances enter the brain due to a compromised blood-brain barrier (BBB).

Neurons deteriorate structurally and functionally as their vulnerability increases. Neural connectivity is hampered by a decrease in neurotransmitter levels, a shrinkage in gray matter volume (especially in areas linked to executive functions), and porous white matter. Dopaminergic neuron depletion impairs cognitive, motor, and sensory processing abilities, further deteriorating brain health.

Advances in Aging Research
Numerous facets of neuronal aging have been discovered by research over the past 70 years, including the buildup of mutations, oxidative stress, immune system deterioration, and the part endogenous retroviruses (ERVs) play in tissue aging. Clinical trials examining metformin’s potential to delay aging have been prompted by genetic studies that have identified mutations like AGE-1 and Daf-2 in Caenorhabditis elegans that significantly extend lifespan.

Longer lifespans have been associated with proteins such as sirtuin 1 (SIRT1) and sirtuin 4 (SIRT4), and yeast longevity has been shown to increase by 70% when SIRTs are activated by small molecules. Rapamycin, which blocks the mTOR pathway, has also demonstrated potential for increasing mammalian longevity through lowering protein accumulation and encouraging autophagy.

Fecal microbiota transplants (FMT), senescent cell removal, and young plasma infusion are other experimental anti-aging methods that have been demonstrated to enhance cognitive function in patients with mild cognitive impairment (MCI) and Parkinson’s disease (PD). Additionally, biological aging—a more accurate measure of physiological aging than chronological age can now be assessed thanks to DNA methylation-based aging clocks.

Integrated Anti-Aging Strategies for NDD Prevention
The intricate relationship between aging and NDDs necessitates a multifaceted strategy. Because the brain is closely related to other bodily systems, therapies that focus on immune, hepatic, and cardiovascular health may reduce the risk of NDD. Maintaining gut health helps avoid toxic protein accumulation and systemic inflammation while improving cardiovascular function enhances the delivery of oxygen and nutrients to the brain.

Recent studies emphasize how viral infections, like SARS-CoV-2, can hasten aging and raise an older adult’s risk of developing NDD. Preventive measures that strengthen the immune system and lessen chronic inflammation are therefore essential. Promising Anti-Aging Therapies: Some possible interventions have been investigated to prevent or slow down NDDs.

Blood-Derived Anti-Aging Molecules: These substances enhance motor function, preserve dopaminergic neurons, detoxify toxic proteins, and encourage neurogenesis. Pharmacological Strategies: Preclinical studies have demonstrated the potential of medications such as metformin, GLP-1 receptor agonists, and senolytics, which eliminate senescent cells.

Biological Therapies: Methods like stem cell transplants, gut microbiome rejuvenation through FMT, and young plasma infusions may help halt age-related decline. Targeted Pathway Modulation: By decreasing undesirable protein accumulation and enhancing cellular resilience, rapamycin-induced mTOR pathway inhibition or SIRT protein activation may shield neurons.

Immunotherapies: In addition to established anti-aging measures, antibody-based therapies that target misfolded proteins are being researched. Even though the results of some trials have been inconsistent, research is still being done to improve these tactics and increase their efficacy. Before these strategies are used in clinical settings, larger, longer-term studies are required to validate them.

Neurodegenerative diseases result from a general imbalance in the body’s intricate adaptive systems rather than a single molecular or cellular malfunction. This emphasizes the necessity of coordinated interventions that target several aging-related mechanisms. An all-encompassing strategy that incorporates cognitive training, a nutritious diet, frequent exercise, and anti-inflammatory techniques can help reduce inflammation, improve respiratory and cardiovascular health, and slow neurodegeneration. To develop a comprehensive approach to preventing, treating, and possibly reversing NDDs, these preventive measures should ideally be paired with disease-specific therapies and the management of coexisting conditions.

Low-carb diets may increase colorectal cancer risk

Low-carb diets may increase colorectal cancer risk

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In recent years, the number of children, teens, and young adults with colorectal cancer has increased. To determine whether the gut microbiota and diet have an effect on the development of colorectal cancer, researchers recently investigated various diets and bacteria. To determine whether there were any effects on the gut, the researchers paired three distinct bacterial strains with three different diets. They discovered that a certain strain of Escherichia coli in conjunction with a low-carb, low-fiber diet can cause an increase in colon polyps, which can result in the development of colorectal cancer.

Although low-carb diets, like the ketogenic diet, have become more popular recently, many experts question whether a more restrictive diet could have detrimental effects on one’s health. In a recent study, researchers from the University of Toronto in Canada investigated the potential effects of low-carb diets on bacteria associated with colorectal cancer. In their study, the researchers employed mice and examined various bacterial strains as well as low-carb, typical, and Westernized diets.

They concentrated on whether these diets have an effect on specific bacteria and how that could lead to the development of colorectal cancer. The findings of their study demonstrated that low-carb diets have a detrimental effect on a particular strain of Escherichia coli. The researchers discovered that it accelerated the growth of polyps. Certain polyps can progress to colorectal cancer.

How might certain bacteria lead to cancer?
One of the most common types of cancer diagnosed in the US is colorectal cancer, which affects the colon and rectum. One out of every 26 women and one out of every 24 men will develop this cancer. According to recent data, the number of colorectal cancer cases among adults aged 30 to 34 increased by 71% between 1999 and 2020, while the number among adults aged 35 to 39 increased by 58% during the same period. The 5-year survival rate for colorectal cancer is 64.4%, according to the Centers for Disease Control and Prevention (CDC)Trusted Source.

Although prevention of colorectal cancer cannot be guaranteed, there are steps people can take to reduce their risk (Trusted Source). Among these are quitting smoking, consuming less alcohol, eating a diet rich in fruits, vegetables, and whole grains, and avoiding processed foods and red meat.

The new study sought to ascertain whether there was a relationship between particular diet types and particular types of bacteria, as researchers suspect that dietary choices may be linked to the development of colorectal cancer. Three bacteria were the focus of their investigation: Helicobacter hepaticus, E. coli, and Bacteroides fragilis.

They colonized the mice using E. Coli. According to the study’s authors, these microbes either directly damage intestinal epithelial cells’ DNA by producing genotoxins or indirectly by inducing inflammatory mediators that damage DNA. The mice used in the study were fed Western-style diets, which were heavy in fat and sugar, regular chow diets, and diets low in carbs and fiber.

E. coli and low-carb diets increase cancer risk
Following nine weeks of feeding the mice their particular diets, the researchers monitored the mice for the development of polyps and remeasured them at sixteen weeks. Only the combination of the low-carb diet and E was tested among the bacteria and diets. Coli may raise the risk of colorectal cancer, according to research. This is noteworthy because, as stated by the authors of the study, E. Coli is found in 60% of cases of colorectal cancer.

This combination increased the number of tumors and polyps in the mice, which can raise the risk of colorectal cancer. These mice also displayed other indicators that increase the risk of colorectal cancer, including DNA damage. The colon’s protective mucous layer against bacteria was weakened by the low-carb diet. In mice that have E. Colibactin was able to reach colon cells because of this. One genotix that harms DNA is colibactin, according to a reliable source.

Additionally, these mice had cell senescence, which can lead to the development of cancer. The mice on low-carb, low-fiber diets with E had reduced levels of gut health regulation, the researchers discovered. coli, which fuels inflammation. In general, mice fed a low-carb diet paired with E. Coli’s gut microbiome was so disturbed and damaged that scientists discovered it to be a setting that encourages colorectal cancer.

Despite these alarming findings, the researchers discovered that feeding these mice fiber decreased the development of tumors and assisted in regulating inflammation. By figuring out whether particular fiber types are more protective and researching their effects on people, the researchers hope to carry on this line of inquiry.

What dietary changes may help lower cancer risk?
According to the article’s highlighted mouse study, there may be a substantial connection between low-carb diets and colibactin-producing E. She informed us about colorectal cancer and E. Coli. A low-carb diet combined with an E. strain was found to be beneficial by the researchers. Mice with colibactin-producing E. Coli developed colorectal cancer. Cusick described how the low-carb, low-fiber diet and E. coli create an environment in the gut. Coli resulted in a thinner mucous barrier, more polyps, which are cancer precursors, and increased gut inflammation.

Although she described the results as fascinating and captivating, she pointed out that more study is required before they can be used on people. Cusick listed a few forms of fiber that might support the colon’s mucus barrier because the study emphasized how important it is.

According to the article’s highlighted mouse study, there may be a substantial connection between low-carb diets and colibactin-producing E. She informed us about colorectal cancer and E. Coli. A low-carb diet combined with an E. strain was found to be beneficial by the researchers. Mice with colibactin-producing E. Coli developed colorectal cancer.

Cusick described how the low-carb, low-fiber diet and E. coli create an environment in the gut. Coli resulted in a thinner mucous barrier, more polyps, which are cancer precursors, and increased gut inflammation. Although she described the results as fascinating and captivating, she pointed out that more study is required before they can be used on people. Cusick listed a few forms of fiber that might support the colon’s mucus barrier because the study emphasized how important it is.

Vora was also not involved in the study. “I believe this can be considered hypothesis-generating,” Vora said of the research. The incidence of colorectal cancer may be explained by a real connection. Although Vora agreed that more research is needed on this subject, he also noted that the gut biome is a popular area of study due to its connection to colon cancer and that many new research topics will emerge in this area.

Aspirin may prevent cancer metastasis by boosting the immune response

Aspirin may prevent cancer metastasis by boosting the immune response

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Approximately 50% of individuals will receive a cancer diagnosis at some point in their lives, usually in their later years. Although cancer cells can separate and spread to other parts of the body, it is easiest to treat cancer that is contained in its original location. By strengthening the body’s immune response, aspirin may help prevent metastases, or secondary tumors, according to researchers looking into how cancer spreads. Aspirin assisted immune cells in eliminating cancer cells that were spreading in their mouse study. People are being studied to see if aspirin or medications that target the same pathway can help prevent or postpone the recurrence of cancers.

Based on data from 2010-2011, Cancer Research UK reports that half of all people in Wales and England who receive a cancer diagnosis will live for at least ten years following their diagnosis. For some of the more common cancers, the percentage is significantly higher. According to data from 2013 to 2017, over 75% of people in England who have been diagnosed with either prostate or breast cancer will still be alive ten years later. Early detection, before the cancer has a chance to spread from its original site, is essential to a successful outcome. Over 90% of cancer-related deaths occur after the disease has spread to another area of the body.

Researchers from the University of Cambridge in the United Kingdom have now found that aspirin, a widely accessible and inexpensive pain reliever, may be able to stop the spread of some cancers. Aspirin affected platelets, which are tiny cells that cause blood to clot, in mice by reducing their production of thromboxane A2 (TXA2), a clotting factor that inhibits immune T cells, according to a study published in Nature. These T cells can then eliminate any cancer cells that are spreading because TXA2 isn’t suppressing them as much.

The study generates a valid hypothesis on how to prevent cancer recurrence and spread using a very simple intervention for patients, according to Nilesh Vora, MD, a board-certified hematologist and medical oncologist who serves as the medical director of the MemorialCare Todd Cancer Institute at Long Beach Medical Center in Long Beach, CA. This article’s main point is that aspirin stops cancers from spreading by lowering TXA2 and releasing suppressed T cells. Although treatment for early-stage cancers has advanced significantly, if cancer cells have spread from the original tumor site, there is still a chance that the cancer will recur elsewhere in the body.

The immune system is weakened inside the original tumor’s microenvironment, making it less effective at eliminating cancer cells. However, the immune system may target these lone cancer cells once they migrate. There is a special window of opportunity for treatment when cancer first spreads because cancer cells are more susceptible to immune attack. Patients with early cancer who are at risk of recurrence should benefit greatly from therapies that target this window of vulnerability.

Surprising new use for old drug
In mice, the researchers had previously discovered 15 genes that affected the spread of cancer. They discovered that some primary cancers in the liver and lungs metastasized less frequently in mice deficient in a gene that produces the protein ARHGEF1. They deduced from this that ARHGEF1 inhibits T cells that eliminate metastatic cells. They then found that when cells are exposed to the clotting factor TXA2, this gene is activated. Although recent evidence now contradicts the data on heart attack and stroke prevention, aspirin is sometimes taken at low doses to lower the risk of blood clots, heart attacks, and strokes because it inhibits platelets’ production of TXA2.

Aspirin-treated mice experienced fewer metastases than control mice in the current study, which examined the mouse model of melanoma, an aggressive type of skin cancer. The aspirin allowed their T cells to kill cancer cells by releasing them from TXA2-induced suppression. According to a press release from Jie Yang, PhD, one of the study co-authors based at the University of Cambridge, It was a eureka moment when we found TXA2 was the molecular signal that activates this suppressive effect on T cells. Yang stated that before this, we were unaware of the significance of our findings in comprehending aspirin’s anti-metastatic action. It was a shocking discovery that led us in a completely different direction than we had originally intended.

Do the findings on aspirin and cancer also apply to people?
Yang emphasized the promise of the research team’s findings, pointing out that aspirin or other medications that might target this pathway might be more affordable than antibody-based treatments and, as a result, more widely available. However, the researchers caution that aspirin can have side effects and may not be suitable for everyone. Aspirin frequently causes indigestion, nausea, and irritation of the stomach or gut. Less frequent adverse effects include bruising, vomiting, stomach bleeding or inflammation, and worsening asthma symptoms. Rarely, it can result in hemorrhagic stroke, kidney failure, or brain bleeding, especially in people who take a daily dose.

The results were welcomed by Anton Bilchik, MD, PhD, a surgical oncologist who was not involved in this study. He is the Chief of Medicine and Director of the Gastrointestinal and Hepatobiliary Program at Providence Saint John’s Cancer Institute in Santa Monica, CA. However, he informed MNT that these findings must first be confirmed in clinical trials involving human subjects. It is necessary to assess aspirin as an adjuvant to immunotherapy and chemotherapy in patients with more advanced cancers as well as aspirin alone in patients with earlier cancers who are not candidates for these treatments.

The good news is that human clinical trials have begun. To determine whether aspirin can prevent or postpone the recurrence of early-stage cancers, the researchers will work with Ruth Langley, MD, professor of oncology and clinical trials in the MRC Clinical Trials Unit at University College London, who is in charge of the Add-Aspirin clinical trial. According to Langley, who was not involved in the current study, people should only begin taking aspirin on a doctor’s recommendation. A small percentage of people may experience severe side effects from aspirin, such as stomach ulcers or bleeding. She underlined that it is crucial to know which cancer patients are most likely to benefit and to always consult your doctor before beginning aspirin.

What is Invokana?

What is Invokana?

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Invokana is a brand-name prescription drug. It’s FDA-approved for use in adults with type 2 diabetes to:

Improve blood sugar levels. For this use, Invokana is prescribed in addition to diet and exercise to lower blood sugar levels. Reduce the risk of certain cardiovascular problems. For this use, Invokana is given to adults with known cardiovascular disease. It’s used to lower the risk of heart attack and stroke that don’t lead to death. The drug is used to reduce the risk of death from a heart or blood vessel problem.
Reduce the risk of certain complications in people who have diabetic nephropathy with albuminuria. For this use, Invokana is given to certain adults who have diabetic nephropathy (kidney damage that’s caused by diabetes) with albuminuria* of greater than 300 milligrams per day. It’s used to lower the risk of:
End-stage kidney disease
death caused by a heart or blood vessel problem
doubled blood level of creatinine
the need to be hospitalized for heart failure
For more information about these uses of Invokana and certain limitations of its use, see the “Invokana uses” section below.

  • With albuminuria, you have high levels of a protein called albumin in your urine.

Drug details
Invokana contains the drug canagliflozin. It belongs to a class of drugs called sodium-glucose co-transporter 2 (SGLT-2) inhibitors. (A drug class describes a group of medications that work similarly.)

Invokana comes as a tablet that’s taken by mouth. It’s available in two strengths: 100 mg and 300 mg.

Effectiveness
For information on Invokana’s effectiveness for its approved uses, see the “Invokana uses” section below.

Invokana generic
Invokana contains one active drug ingredient: canagliflozin. It’s available only as a brand-name medication. It’s not currently available in generic form. (A generic drug is an exact copy of the active drug in a brand-name medication.)

Invokana side effects
Invokana can cause mild or serious side effects. The following list contains some key side effects that may occur while taking Invokana. This list doesn’t include all possible side effects.

To learn more about possible side effects of Invokana or how to manage them, talk with your doctor or pharmacist.

Note: The Food and Drug Administration (FDA) tracks side effects of drugs it has approved. If you would like to notify the FDA about a side effect you’ve had with Invokana, you can do so through MedWatch.

More common side effects
The more common side effects of Invokana can include*:

urinary tract infections / urinating more often than normal / thirstiness / constipation / nausea / yeast infections† in men and women / vaginal itching.

Most of these side effects may go away within a few days or a couple of weeks. If they’re more severe or don’t go away, talk with your doctor or pharmacist. You should also call your doctor if you think you have a urinary tract infection or yeast infection.

  • This is a partial list of more common side effects from Invokana. To learn about other mild side effects, talk with your doctor or pharmacist or visit Invokana’s medication guide.
    † For more information about this side effect, see the “Side effect details” section just below.

Serious side effects
Serious side effects from Invokana aren’t common, but they can occur. Call your doctor right away if you have serious side effects. Call 911 if your symptoms feel life-threatening or if you think you’re having a medical emergency.

Serious side effects and their symptoms can include the following:

Dehydration (low fluid level), which can cause low blood pressure. Symptoms can include:
dizziness/feeling faint/lightheadedness/weakness, especially when you stand up
Hypoglycemia (low blood sugar level). Symptoms can include:
drowsiness/headache/confusion/weakness/hunger/irritability/sweating/feeling jittery/fast heartbeat
Severe allergic reaction.*
Amputation of lower limbs.*
Diabetic ketoacidosis (increased levels of ketones in your blood or urine).*
Fournier’s gangrene (severe infection near the genitals).*
Kidney damage.* Bone fractures.*

Side effect details
You may wonder how often certain side effects occur with this drug. Here’s some detail on certain side effects this drug may or may not cause.

Allergic reaction
As with most drugs, some people can have an allergic reaction after taking Invokana. In clinical studies, up to 4.2% of people taking Invokana reported having mild allergic reactions.

Symptoms of a mild allergic reaction can include:

skin rash/itchiness/flushing (warmth, swelling, or redness in your skin)
A more severe allergic reaction is rare but possible. Only a few people in clinical studies reported severe allergic reactions while taking Invokana.

Symptoms of a severe allergic reaction can include:

swelling under your skin, typically in your eyelids, lips, hands, or feet
swelling of your tongue, mouth, or throat/trouble breathing
Call your doctor right away if you have a severe allergic reaction to Invokana. But call 911 if your symptoms feel life-threatening or if you think you’re having a medical emergency.

Amputation
Invokana may increase your risk of amputation of lower limbs. (With amputation, one of your limbs is removed.)

Two studies found an increased risk for lower limb amputation in people who took Invokana and had:

type 2 diabetes and heart disease, or
type 2 diabetes and were at risk for heart disease
In the studies, up to 3.5% of the people who took Invokana had an amputation. Compared with people who didn’t take the drug, Invokana doubled the risk of amputation. The toe and the midfoot (arch area) were the most common areas of amputation. Some leg amputations were also reported.

Before you start taking Invokana, talk with your doctor about your risk of amputation. This is especially important if you’ve had an amputation in the past. It’s also important if you have a blood circulation or nerve disorder, or diabetic foot ulcers.

Call your doctor right away and stop taking Invokana if you:

feel new foot pain or tenderness
have foot sores or ulcers
get a foot infection
Call 911 if your symptoms feel life-threatening or if you think you’re having a medical emergency. If you develop symptoms or conditions that increase your risk for lower limb amputation, your doctor may have you stop taking Invokana.

Yeast infection
Taking Invokana increases your risk of a yeast infection. This is true for both men and women, according to data from clinical trials. In the trials, up to 11.6% of the women and 4.2% of the men had a yeast infection.

You’re more likely to develop a yeast infection if you’ve had one in the past or if you’re an uncircumcised male.

If you get a yeast infection while taking Invokana, talk with your doctor. They can suggest ways to treat it.

Diabetic ketoacidosis
Although it’s rare, some people who take Invokana can develop a serious condition called diabetic ketoacidosis. This condition occurs when cells in your body don’t get the glucose (sugar) they need for energy. Without this sugar, your body uses fat for energy. And this can lead to high levels of acidic chemicals called ketones in your blood.

Symptoms of diabetic ketoacidosis can include:

excessive thirst/urinating more often than normal/nausea/vomiting/stomach pain/tiredness/weakness/shortness of breath/breath that smells fruity/confusion
In severe cases, diabetic ketoacidosis can cause coma or death. If you think you may have diabetic ketoacidosis, call your doctor right away. But if your symptoms are severe, call 911 or go to the nearest emergency room.

Before you start taking Invokana, your doctor will assess your risk for developing diabetic ketoacidosis. If you have an increased risk of this condition, your doctor may monitor you closely during treatment. And in some cases, such as if you’re having surgery, they may have you temporarily stop taking Invokana.

Fournier’s gangrene
Fournier’s gangrene is a rare infection in the area between your genitals and rectum. Symptoms can include:

pain, tenderness, swelling, or reddening in your genital or rectal area
fever malaise (overall feeling of discomfort)
People in clinical trials of Invokana didn’t get Fournier’s gangrene. However after the drug was approved for use, some people reported having Fournier’s gangrene while taking Invokana or other drugs in the same drug class. (A class of drugs describes a group of medications that work in the same way.)

More serious cases of Fournier’s gangrene have led to hospitalization, multiple surgeries, or even death.

If you think you may have developed Fournier’s gangrene, call your doctor right away. They may want you to stop taking Invokana. They will also recommend treatment for the infection.

Kidney damage
Taking Invokana can increase your risk of kidney damage. Symptoms of kidney damage can include:

urinating less often than normal
swelling in your legs, ankles, or feet
confusion
fatigue (lack of energy)
nausea
chest pain or pressure
irregular heartbeat
seizures
After the drug was approved for use, some people taking Invokana reported that their kidneys worked poorly. When these people stopped taking Invokana, their kidneys began to work normally again.

You’re more likely to have kidney problems if you:

are dehydrated (have a low fluid level)
have kidney or heart problems
take other medications that affect your kidneys
are older than age 65
Before you start taking Invokana, your doctor will test how well your kidneys are working. If you have kidney problems, you may not be able to take Invokana.

Your doctor may also test how your kidneys are working during your treatment with Invokana. If they detect any kidney problems, they may change your dose or stop your treatment with the drug.

Bone fractures
In a clinical study, some people who took Invokana experienced bone fractures (broken bones). The fractures weren’t usually severe.

Symptoms of bone fracture can include:

pain/swelling/tenderness/bruising/deformity
If you’re at high risk for a fracture or if you’re concerned about breaking a bone, talk with your doctor. They can suggest ways to help prevent this side effect.

Falls: In nine clinical trials, up to 2.1% of people who took Invokana had a fall. There was a higher risk of falls in the first few weeks of treatment.

If you have a fall while taking Invokana or if you’re concerned about falling, talk with your doctor. They can suggest ways to help prevent this side effect.

Pancreatitis (not a side effect)

Pancreatitis (inflammation in your pancreas) was extremely rare in clinical trials. Rates of pancreatitis were similar between people who took Invokana and those who took a placebo (treatment without active drug). Because of these similar results, it’s not likely that Invokana caused the pancreatitis.

If you have concerns about developing pancreatitis with Invokana, talk with your doctor.

Joint pain (not a side effect): Joint pain wasn’t a side effect of Invokana in any clinical trials.

However, some other diabetes drugs may cause joint pain. In fact, the Food and Drug Administration (FDA) released a safety announcementTrusted Source for a class of diabetes drug called dipeptidyl peptidase-4 (DPP-4) inhibitors. (A drug class describes a group of medications that work in the same way.) The announcement said that DPP-4 inhibitors may cause severe joint pain.

But Invokana doesn’t belong to that drug class. Instead, it belongs to a class of drugs called sodium-glucose co-transporter-2 (SGLT2) inhibitors.

If you have concerns about joint pain with Invokana use, talk with your doctor.

Hair loss (not a side effect)/Hair loss wasn’t a side effect of Invokana in any clinical trials.

If you’re concerned about hair loss, talk with your doctor. They can help you determine what’s causing it and ways to treat it.

Invokana dosage
The Invokana dosage your doctor prescribes will depend on several factors. These include:

the type and severity of the condition you’re using Invokana to treat
your age
other medical conditions you may have
how well your kidneys are working
certain other medications you may be taking with Invokana
Typically, your doctor will start you on a low dosage. Then they’ll adjust it over time to reach the amount that’s right for you. Your doctor will ultimately prescribe the smallest dosage that provides the desired effect.

The following information describes dosages that are commonly used or recommended. However, be sure to take the dosage your doctor prescribes for you. Your doctor will determine the best dosage to suit your needs.

Drug forms and strengths
Invokana comes as a tablet. It’s available in two strengths:

100 milligrams (mg), which comes as a yellow tablet
300 mg, which comes as a white tablet
Dosage for lowering blood sugar levels
Recommended dosages of Invokana to lower blood sugar levels are based on a measurement called estimated glomerular filtration rate (eGFR). This measurement is done using a blood test. And it shows how well your kidneys are working.

In people with an:

eGFR of at least 60, they have no loss of kidney function to mild loss of kidney function. Their recommended dosage of Invokana is 100 mg once daily. Their doctor may increase their dosage to 300 mg once daily if needed to help manage their blood sugar level.
eGFR of 30 to less than 60, they have mild-to-moderate loss of kidney function. Their recommended dosage of Invokana is 100 mg once daily.
eGFR of less than 30, they have severe loss of kidney function. It’s not recommended that they begin using Invokana. But if they’ve already been using the drug and are passing a certain level of albumin (a protein) in their urine, they may be able to continue taking Invokana.*
Note: Invokana shouldn’t be used by people who are using dialysis therapy. (Dialysis is a procedure that’s used to clear waste products from your blood when your kidneys aren’t healthy enough to do so.)

  • For this use, people would be taking Invokana at a dosage of 100 mg to lower the risk of certain complications of diabetic nephropathy. See the “Invokana uses” section for more information.

Dosage for reducing cardiovascular risks
Recommended dosages of Invokana to reduce cardiovascular risks are the same as they are to lower blood sugar levels. See the section above for details.

Dosage for reducing the risk of complications from diabetic nephropathy
Recommended dosages of Invokana to lower the risks of complications from diabetic nephropathy are the same as they are to lower blood sugar levels. See the section above for details.

What if I miss a dose?
If you miss a dose of Invokana, take it as soon as you remember. If it’s almost time for your next dose, skip the missed dose and take the next dose at the normal time. Don’t try to catch up by taking two doses at once. This can cause dangerous side effects.

Using a reminder tool can help you remember to take Invokana every day.

Be sure to take Invokana only as your doctor prescribes.

Will I need to use this drug long-term?
If you and your doctor agree that Invokana is working well for you, you’ll likely use it long-term.

New test may predict which IBD patients have higher colorectal cancer risk

New test may predict which IBD patients have higher colorectal cancer risk

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Individuals who suffer from inflammatory bowel disease (IBD) are more likely to develop colorectal cancer. Every one to three years, people with IBD frequently undergo colonoscopies to screen for colorectal cancer. Previous studies have demonstrated that identifying precancerous cells in individuals with IBD can be difficult. A new test created by researchers at London’s Institute of Cancer Research claims to be able to predict bowel cancer risk in individuals with IBD with 90% accuracy. According to earlier studies, individuals with inflammatory bowel disease (IBD), which includes Crohn’s disease and ulcerative colitis, are more likely to develop colorectal cancer than those without IBD.

Due to the chronic inflammation associated with IBD, which can lead to the growth of abnormal cells called dysplasia and the development of precancerous polyps in the intestinal tract, people with IBD are more likely to develop colorectal cancer, also known as bowel cancer. Currently, a colonoscopy is performed every one to three years to screen for colorectal cancer in individuals with IBD. Nevertheless, prior research indicates that it can be challenging to identify precancerous cells in IBD patients. Researchers at London’s Institute of Cancer Research have now created a new test that they claim can more than 90% accurately predict bowel cancer risk in individuals with IBD.

The study’s senior author, Trevor Graham, PhD, a professor of genomics and evolution and director of the Centre for Evolution and Cancer at The Institute of Cancer Research in London, stated that while individuals with IBD are more likely to develop bowel cancer, there is currently no reliable method to predict that risk. Graham told Medical News Today that the only effective treatment for people who are believed to be in imminent danger of developing cancer is surgery to remove part or all of the large bowel. This procedure may save a life. However, people are undergoing needless surgery that can change their lives because we are currently unable to determine whether a patient actually needs the procedure. However, he added, those whose risk of bowel cancer is deemed low and for whom we do not perform surgery still experience anxiety due to the uncertainty surrounding their cancer risk.

Increased risk of cancer with cellular DNA changes
Researchers discovered that individuals with IBD who had precancerous cells that either gained or lost multiple copies of DNA were more likely to develop bowel cancer. The researchers then used the precise pattern of the altered DNA in the precancerous cells to create an algorithm that would predict the risk of colorectal cancer in the future. According to Graham, individuals with IBD in the UK undergo routine colonoscopies, which involve a camera being inserted up their butt to check for early indications of cancer. A biopsy is a tiny sample of tissue taken if something odd is observed. The test we run on the biopsy is a genetic test. According to him, we have developed a test to predict an individual’s risk based on the genetic signals in their biopsy after comparing the genetic signals of those who did and did not develop cancer.

Test predicts colorectal cancer risk with over 90% accuracy
Graham and his colleagues discovered that their novel test could more than 90% accurately predict which IBD study participants who developed precancerous cells would later develop colorectal cancer within five years. Graham stated, “We hope that by accurately identifying those at risk of cancer, we will be able to provide appropriate treatment.”. Surgery can be used to remove the colon and reduce the risk of cancer in people who are at a high risk of getting the disease. We can spare people who are not at high-risk needless anxiety and care. In clinical trials that we intend to conduct in the future, we must demonstrate that our predictions are accurate for patients to benefit from this, he said.

Although bowel cancer is more likely to strike people with inflammatory bowel disease, most IBD patients do not go on to get the disease. By predicting who is actually at risk, our new test enables all patients to receive the best possible care. To demonstrate that our predictions are accurate in practical situations, we will next conduct clinical trials. In the upcoming years, we hope to be able to administer the test within the NHS.

A less invasive predictive test
Regarding this study, a board-certified gastroenterologist at Providence Saint John’s Health Center in Santa Monica, California, commended it as fantastic, outstanding, and wonderful. The truth is that we frequently perform colonoscopies and biopsies on our IBD patients to check for dysplasia or cells or tissue that may develop into cancer. After that, we must have these conversations with them. Bedford clarified, “What do we do if they do have these low-grade dysplastic cells? Do we remove your colon or do we do more frequent surveillance?

It sounds like the speaker is expressing enthusiasm about a new test for predicting cancer risk in patients with inflammatory bowel disease (IBD). A test with 90% accuracy could significantly improve clinical decision-making by identifying those at risk for cancer and allowing doctors to target therapy more effectively. This could reduce the need for invasive procedures, which is always a win for patient comfort and safety. Additionally, if the test could be adapted into a blood or stool test, it would make it even more convenient for patients, potentially improving adherence to monitoring and early intervention.
It’s exciting when advancements like this can make a real difference in patient care! Would you like more information on current developments in diagnostic tests for IBD or related cancer risks?

Determining who is at higher risk
It seems like Dr. Nilesh Vora is also highlighting the potential of this study, emphasizing how valuable it would be for gastroenterologists to have a more accurate way of identifying which patients with inflammatory bowel disease (IBD) are at higher risk for colon cancer. This would help doctors make more informed decisions on how to manage these patients and which individuals might benefit from closer monitoring or more aggressive treatments.

Dr. Vora’s perspective points to the benefit of targeted care by identifying at-risk patients, healthcare providers can potentially avoid unnecessary procedures for those not at risk, while ensuring higher-risk patients are managed more carefully. This kind of approach could streamline care and improve outcomes for patients with IBD, who already face challenges related to their condition.

It’s fascinating to see how medical fields are working together to improve outcomes for patients, and studies like this really highlight how advances in one area of medicine (in this case, diagnostic tools for cancer risk) can have a ripple effect on multiple specialties, improving patient care overall. Does this kind of collaboration between specialists and new diagnostic tests interest you?

That’s a crucial next step! Getting FDA approval for this test would be a significant milestone. If it’s approved, it could become a standard tool in clinical practice, helping doctors more accurately determine which IBD patients need frequent colonoscopies and which could safely extend the interval between screenings. Reducing the number of unnecessary colonoscopies would not only ease the burden on patients but also reduce healthcare costs and free up resources for those who truly need more frequent monitoring.

The potential for a more personalized approach to care where screenings are tailored to an individual’s actual risk—could be a game changer in managing IBD patients. The idea of offering more tailored and less invasive options for ongoing care could improve patient experience, both physically and psychologically.

If the test proves to be both accurate and accessible, it could help revolutionize the way doctors approach cancer prevention and monitoring for IBD patients. What do you think are some of the biggest hurdles in getting something like this approved by the FDA?

Common sleep medication may prevent the brain from clearing ‘waste’

Common sleep medication may prevent the brain from clearing ‘waste’

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Up to 70 million people suffer from persistent sleep problems. A person’s risk of developing dementia and cognitive decline is increased when they don’t get enough sleep each night. Using a mouse model, a new study explains for the first time how the brain’s glymphatic system is powered by synchronized oscillations during sleep to help eliminate “waste” linked to neurodegenerative diseases. Additionally, researchers discovered that a frequently prescribed sleep aid may suppress those oscillations, interfering with the brain’s ability to eliminate waste while you sleep. It’s critical to consider every factor that could increase the risk of cognitive decline, especially in light of recent studies showing that the risk of dementia in Americans has more than doubled after the age of 55.

According to the most recent data, many adults over the age of 18 may experience persistent sleep problems like insomnia and sleep apnea, despite doctors’ recommendations that they get at least 7 hours of good sleep every night. It is estimated that 39 percent of adults over 45 in the United States alone were not getting enough sleep in 2022. According to previous research, a person’s risk of developing some illnesses, including brain-related disorders like dementia and cognitive decline, can be raised by not getting enough sleep each night. Natalie Hauglund, PhD, a postdoctoral fellow at the Universities of Copenhagen in Denmark and Oxford in the United Kingdom, told Medical News Today that sleep enables the brain to go offline, stop processing information from the outside world, and concentrate on maintenance functions like waste removal and immune surveillance. Disease development and cognitive decline are linked to sleep deprivation.

But could some sleep aids also lead to worse brain health as we age? Researching all the potential causes of cognitive decline is more crucial than ever, especially in light of a recent study in Nature Medicine that found that Americans’ risk of developing dementia after the age of 55 has more than doubled compared to previous estimates. For the first time, Hauglund is the first author of a study that uses a mouse model to describe the synchronized oscillations that occur during sleep and power the brain’s glymphatic system, which helps remove waste linked to neurodegenerative diseases. The study was published in the journal Cell. According to the survey, zolpidem, a popular prescription sleep aid sold under Ambien, may suppress these oscillations and interfere with the brain’s ability to eliminate waste while you sleep.

What powers the brain’s ‘waste-removal’ system?
For this study, scientists recorded the brain activity of mice both awake and asleep using a variety of technologies. Researchers found that the brain’s waste-removing glymphatic system is essentially powered by slow, synchronized oscillations of the neurotransmitter norepinephrine, cerebral blood, and cerebrospinal fluid (CSF) during non-REM sleep. The brain uses cerebrospinal fluid, a fluid produced inside the brain, to flush the brain tissue and wash away unwanted molecules. This makes our brain unique because it lacks lymphatic vessels, which remove waste products like dead cells and bacteria from the rest of our body, she explained.

The glymphatic system is the brain’s cleaning mechanism. Crucially, the glymphatic system only activates during non-REM sleep, which is the deepest phase of sleep. This is due to a neuromodulator called norepinephrine, which is released in slow cycles approximately every 50 seconds during non-REM sleep. Nedergaard informed us that norepinephrine causes the arteries to constrict by binding to their muscle cells. Consequently, a gradual fluctuation in the brain’s blood volume and artery diameter is caused by the slow oscillation in norepinephrine concentration. Cerebrospinal fluid is transported through the brain’s tissue and along the arteries by this dynamic change in blood volume, which functions as a pump. She explained that norepinephrine thus controls the glymphatic system by coordinating the synchronized dilatation and constriction of the blood vessels.

Sleep aids may disrupt the brain’s glymphatic system
The possibility that sleep aids could mimic the natural oscillations required for the glymphatic function was also investigated. They concentrated their investigation on zolpidem, a sedative. They found that zolpidem seemed to stop norepinephrine oscillations, which disrupted the brain’s glymphatic system’s ability to remove waste while you slept. Although our research indicates that sleep medication may not have the same positive effects as natural, restorative sleep, sleep aids may offer a shortcut to sleep, according to Hauglund. Our results highlight the importance of using sleep aids sparingly and only as a last resort. Sleep is essential because it allows the brain to complete homeostatic housekeeping functions like eliminating waste. Conversely, sleep aids hinder the brain’s ability to properly prepare for each new day by blocking the neuromodulators that control the waste removal system.

Should sleep-aid users be concerned?
As per Segal’s perspective, not being part of the recent study, the advantages derived from enhanced sleep due to the use of sleep aids like zolpidem seemingly fail to surpass any alleged negative impact this medication may have on decreasing REM sleep, consequently lowering brain neurotransmitter levels, subsequently affecting brain protein levels. The numerous ‘in turn’ assertions do not instill any worry in me that this research holds any substantial clinical relevance, he mentioned. Clinical neurologists, including myself, are not apprehensive about the possibility of zolpidem misuse leading to dementia in the elderly population struggling with insomnia.

It is difficult for clinical neurologists like me to agree that sleeping pills will cause dementia. I would tell my patients that the advantages of getting a good night’s sleep outweigh any potential risks that may arise, such as dementia or memory loss as they age. The relationship between brain health, sleep quality, and general healthPolos, who was not involved in the study, said he found the results intriguing. “There is no question that the glymphatic system can work in synchrony with different transmitters and waste products in the brain,” he said.

According to this study, changes to this delicate balance may have cellular and possibly therapeutic repercussions. Though intriguing, we must keep in mind that this is an animal study and that extrapolating results from it to humans should be done carefully, as is frequently the case. It does, however, provide physicians with a phenomenon that merits some discussion. “We definitely would like to see if studies could assess the impact of sleep aids on human glymphatic flow if more work were to be done in this area,” Polos added. Naturally, noninvasive methods and possibly some sophisticated imaging would be needed for this. Even in small quantities, such data would be useful.

He went on to say that it is impossible to overstate the connection between the brain, restful sleep, and general health. As sleep physicians, we fully support ongoing research into the relationship between the brain, sleep, and general health because the rhythmic nature of sleep and the regular cycling of sleep stages have been thoroughly studied. We have learned a lot about the effects of changes in the brain and how they affect sleep, but we still have a lot to learn.

Alzheimer’s: Are newly approved drugs making a real-life difference?

Alzheimer’s: Are newly approved drugs making a real-life difference?

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In 2021, the Food and Drug Administration (FDA) finally approved some new medications to treat Alzheimer’s disease after a nearly two-decade hiatus. The majority of these medications are antibody treatments that target harmful protein clusters in the brain. Their endorsement has generated equal parts excitement and controversy. In this Special Feature, we look into the fundamental question of whether these medications are actually having an impact. The neurodegenerative condition known as Alzheimer’s disease causes a slow and irreversible loss of thinking, memory, and ultimately the capacity to carry out daily tasks. Alzheimer’s disease is primarily caused by aging, and as the population ages quickly, it has become a public health emergency.

Alzheimer’s disease affected 57 million people worldwide in 2019; by 2050, that figure is predicted to rise to 153 million. This emphasizes the necessity of disease-modifying therapies that alter the course of the illness permanently and slow its progression. The development of disease-modifying treatments for Alzheimer’s disease, however, has not been successful until recently. The beta-amyloid protein, whose aberrant accumulation is generally thought to be the cause of Alzheimer’s disease, has been the focus of the majority of clinical research aimed at creating disease-modifying treatments for the condition. Regarded as the first disease-modifying treatment for Alzheimer’s disease, aucanumab, an antibody that targets amyloid-beta protein deposits, was approved by the Food and Drug Administration (FDA) in 2021.

Nevertheless, aducanumab’s manufacturer, Biogen, announced that it will eventually halt sales after clinical trials failed to yield consistent improvements in cognitive function. Since then, phase 3 clinical trials have shown that two additional anti-amyloid antibodies, lecanemab from Biogen and donanemab from Eli Lily, can slow cognitive decline in people with early-stage Alzheimer’s disease. These antibodies have been approved by the FDA. Clinicians and researchers have welcomed the approval of lecanemab and donanemab as a breakthrough after decades of clinical research that failed to yield effective disease-modifying therapies. The modest clinical benefits of these anti-amyloid treatments have, however, drawn criticism from some researchers who point to safety concerns and a lack of cost-effectiveness.

While there are challenges at the clinical, societal, and healthcare levels, we should not forget the opportunities and the breakthrough that after decades of very costly negative trials, we finally have unequivocal evidence that it is possible to reduce the progression of the disease, said Dag Aarsland, MD, professor of old age psychiatry at King’s College London in the United Kingdom, in an interview with Medical News Today. Paresh Malhotra, PhD, who teaches clinical neurology at Imperial College London in the United Kingdom, is comparable. K. pointed out that even though these anti-amyloid treatments are only moderately effective, it’s crucial to understand that they are the first to show clinical effects that seem to be connected to a major mechanism of disease progression. Their introduction could speed up the development of new treatments and revolutionize clinical services for Alzheimer’s disease, the most prevalent cause of dementia in the world.

The amyloid cascade theory is the foundation for the creation of anti-amyloid antibody therapies like lecanemab and donanemab. This theory states that Alzheimer’s disease develops as a result of additional alterations in the brain brought on by the buildup of beta-amyloid protein. In particular, it is thought that the development of beta-amyloid aggregates causes oxidative stress, inflammation, neuronal damage, the loss of synapses the connections between neurons that enable communication and, eventually, cognitive decline. This is supported by the fact that beta-amyloid protein buildup occurs several years before cognitive function, such as memory and decision-making, deteriorates.

Secretase enzymes cleave a larger amyloid precursor protein to produce the beta-amyloid protein. Each beta-amyloid protein unit is known as a monomer, and these monomers can combine to form oligomers, which are soluble short chains made up of two to more than fifty monomers. Larger, soluble protofibrils and insoluble fibrils can also be formed by the aggregation of beta-amyloid monomers. In the extracellular space between neurons, the insoluble fibrils subsequently come together to form plaques.

Amyloid plaques were once believed to be poisonous and to be the cause of Alzheimer’s disease. However, over the last 20 years, research has indicated that beta-amyloid oligomers are more harmful than amyloid plaques and may be more involved in the onset of Alzheimer’s disease. It is believed that poor production or clearance of beta-amyloid protein is the cause of the buildup of beta-amyloid aggregates. Over the last 20 years, some medications have been created that either target the enzymes that produce beta-amyloid or make it easier to remove beta-amyloid aggregates. However, because of their serious side effects or inability to produce the intended clinical effects, these medications have failed to obtain FDA approval.

The only FDA-approved treatments that target beta-amyloid aggregates are the anti-amyloid antibodies lecanemab, aducanumab, and donanemab. The affinity of these antibodies for the different kinds of beta-amyloid protein aggregates varies. While aducanumab and lecanemab bind to beta-amyloid oligomers, protofibrils, and plaques, donanemab binds to a particular type of beta-amyloid that is exclusively present in plaques. While aducanumab has a greater affinity for insoluble fibrils, lecanemab exhibits the highest affinity for beta-amyloid protofibrils.

Activating an immune response against beta-amyloid aggregates and causing their removal is one of the hypothesized mechanisms by which anti-amyloid antibodies generate their therapeutic effects. Additionally, anti-amyloid antibodies may neutralize the plaques by binding to oligomers or destabilizing them. In 2021, the FDA gave aducanumab accelerated approval for the treatment of Alzheimer’s disease because of its capacity to remove amyloid plaques. Although aducanumab was effective in removing amyloid plaques from the brain, different clinical trials showed different effects on cognitive function.

The FDA’s approval process caused controversy, and doctors were reluctant to prescribe aducanumab because of the lack of evidence supporting its therapeutic effects. Additionally, as was already mentioned, Biogen has halted aducanumab’s development and sales as of 2024. On the other hand, lecanemab and donanemab have both demonstrated the capacity to remove amyloid plaques while delaying the course of the illness. People with early-stage Alzheimer’s disease and lower baseline beta-amyloid levels respond better to these treatments. The FDA has approved the intravenous infusion of lecanemab and donanemab for use in patients with early-stage Alzheimer’s disease, including those with mild cognitive impairment or mild Alzheimer’s disease.

Donanemab must be administered every four weeks, while lecanemab should be given every two weeks. Donanemab’s ability to allow patients to stop treatment once they have achieved total plaque clearance is one of its special qualities. Amyloid plaques develop over some years, and it is thought that people may only need minor additional care. Lecanemab and donanemab phase 3 trial participants demonstrated slower declines in cognitive function by 27% and 36%, respectively, when compared to placebo.

These results, according to some researchers, are mild and on par with symptomatic treatments like acetylcholinesterase inhibitors, which reduce symptoms without altering the course of the illness. Additionally, the Clinical Dementia Rating Sum of Boxes (CDR-SB) was used to measure the cognitive changes mentioned above. Additionally, when comparing the anti-amyloid antibody treatment groups to the placebo group, researchers found that the absolute difference in decline in cognitive function, as measured by the difference in scores on the CDR-SB scale, did not indicate a clinically significant effect of these anti-amyloid therapies.

Donanemab treatment only resulted in a 14–8% slower decline in cognitive function, according to more objective measures of cognition like the Mini-Mental State Examination [MMSE]. Stated differently, it has been suggested that the evidence currently available indicates that the clinical benefit of these anti-amyloid medications may be minimal. These medications’ effectiveness only results in a statistically significant but clinically meaningless slower decline rather than improvements. The clinical advantages of anti-amyloid antibodies, according to some researchers, support the amyloid cascade theory. Others, however, contend that there are still a lot of unanswered questions, making this conclusion premature.

The amyloid-beta hypothesis states that Alzheimer’s disease should have progressed more slowly as a result of aducanumab’s capacity to remove plaque. Nevertheless, detractors contend that aducanumab trials demonstrated efficient amyloid plaque removal without consistently yielding therapeutic benefits. Similarly, donanemab only caused a 14–8% slower decline in cognitive function as determined by MMSE scores, despite removing roughly 85% of plaques from patients in the phase III trial. Crucially, the amyloid cascade theory served as the foundation for the FDA’s decision to approve aducanumab. The buildup of tau protein within neurons is another aspect of Alzheimer’s disease, and the degree of tau accumulation—rather than beta-amyloid—is linked to the severity of cognitive decline.

The notion that beta-amyloid plays a key role in the development and progression of Alzheimer’s disease is being leveraged by pharmaceutical interventions that aim to reduce beta-amyloid or its production. Many people have contested this theory. Additionally, the outcomes of clinical trials for these drugs show a high associated risk and little efficacy. Therefore, some researchers contend that the modest effectiveness of anti-amyloid antibodies suggests that the beta-amyloid pathway contributes to the development of Alzheimer’s disease along with other pathways, rather than suggesting that the beta-amyloid pathway plays a focal role in the disease’s development.

This theory holds that Alzheimer’s disease develops as a result of a complex network of factors, including those linked to the environment, oxidative stress, inflammation, metabolic factors, and genes unrelated to the amyloid pathway. This perspective also suggests that anti-amyloid treatments, when used in conjunction with other therapies, may play a part in the treatment of Alzheimer’s disease. On the other hand, beta-amyloid aggregation might be a sign of other compromised biological pathways or a downstream phenomenon. According to Perlmutter, it is now evident that the activation of the brain’s microglial cells is largely dependent on metabolic dysfunction upstream of amyloid plaque formation. This phenotypic shift both promotes the formation of beta-amyloid and decreases its degradation.

Furthermore, microglial activation causes synaptic degradation and jeopardizes neuron viability, two key characteristics of Alzheimer’s disease. As has now been shown in early research employing GLP-1 agonists, treatments that target brain metabolism will therefore probably offer significant benefits for Alzheimer’s disease, Perlmutter continued. It is necessary to balance the risks, expenses, and accessibility of anti-amyloid antibody therapies against the limited clinical benefits they offer. A considerable percentage of participants in the phase 3 clinical trials for lecanemab (45%) and donanemab (89%) experienced adverse effects.

For example, amyloid-related imaging abnormalities (ARIA) are alterations in the brain that frequently occur in patients receiving anti-amyloid antibody treatments. These changes, which include either small areas of bleeding from blood vessel rupture (microhemorrhage) or brain swelling (edema), are seen during routine follow-up magnetic resonance imaging (MRI) scans. In the phase 3 trials, for example, ARIA was observed in 21 percent and 36 percent of patients treated with lecanemab and donanemab, respectively. The majority of ARIA cases are asymptomatic and go away in ten weeks.

Even though ARIA symptoms are usually mild to moderate, there have been reports of serious side effects like seizures and even death. In the phase III donanemab clinical trial, for example, approximately 1 in 6 participants experienced severe adverse effects related to ARIA, while the donanemab group experienced a death rate of 0 in 35. The long-term consequences of amyloid-related imaging abnormalities, even those that are mild to moderate in severity, are unknown, in addition to worries about these grave side effects. Adverse effects like nausea, fever, rash, and dizziness are also linked to the infusion of these anti-amyloid antibodies.

Of patients treated with lecanemab and donanemab, respectively, 24 and 8 percent experienced such infusion-related reactions. Regular MRI scans and clinical follow-ups are required due to these amyloid-related imaging abnormalities and other side effects. In the phase III trials for lecanemab and donanemab, people who had at least one copy of the APOE4 gene a gene associated with an increased risk of Alzheimer’s disease—were more likely to experience brain swelling.

Additionally, these medications were less effective in people who had one or more copies of APOE4. Therefore, before beginning anti-amyloid therapy, people must undergo genetic screening. Anti-amyloid immunotherapies are also linked to an increase in the volume of the brain’s fluid-filled ventricles and a decrease in the volume of the entire brain. Reduced cognition is linked to both a decrease in the volume of the entire brain and an increase in the volume of the ventricles. It’s unclear, though, if these alterations in brain volume and cognitive function are causally related. Therefore, it is necessary to investigate the effects of these alterations in brain volume following anti-amyloid therapies. It’s interesting to note that donanemab treatment led to a lesser decrease in the volume of the hippocampus, a part of the brain essential for memory and learning.

It is unlikely that many people with Alzheimer’s disease will fit the requirements to be enrolled in lecanemab or donanemab clinical trials. These studies’ participants were younger and had fewer co-occurring illnesses. Therefore, treating a real-world population of people with Alzheimer’s and co-occurring conditions is likely to result in more side effects or decreased effectiveness. The healthcare system faces additional challenges in diagnosing and screening patients who qualify for anti-amyloid therapies, in addition to managing side effects.

The majority of people with Alzheimer’s disease are not identified until the disease is advanced, and early detection would necessitate screening a large number of people with imaging tests or measuring biomarkers in cerebrospinal fluid. Therefore, widespread availability would require a significant financial outlay for APOE4 genetic testing, early Alzheimer’s disease screening, and diagnosis, and the monitoring and treatment of ARIAs and infusion-related reactions, regardless of their severity. A third of dementia patients in the UK do not receive a diagnosis at all, and certain diagnostic tests are necessary to confirm eligibility for new treatment. To make sure that those who qualify for new treatments can get them when they work best, which seems to be in the early stages of Alzheimer’s disease, we need to invest in diagnostic infrastructure and personnel.

Common Medications for Other Conditions in People with Lupus

Common Medications for Other Conditions in People with Lupus

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Lupus is an autoimmune disease that causes the body’s immune system to attack healthy tissue. This inflammation can affect many parts of the body, including the skin, joints, heart, lungs, and kidneys. Lupus can be a life-threatening disease, but with the right care and treatments, individuals can live long, happy, and healthy lives. Most often, serious issues come from heart disease, kidney failure, or infections.

Doctors often use The following medications to treat other conditions that commonly occur in people with lupus. Although these drugs do not specifically address the underlying cause of lupus, they are used to treat other conditions that may be compounded or indirectly caused by lupus. Since lupus affects people differently, treatment courses are highly individualized. Please remember to take your medications exactly as directed by your physician and notify him/her of any concerns upon your next visit. Never take any medications until they are approved by your doctor – in other words, do not self-medicate!

Aspirin Low doses of aspirin are often recommended for lupus patients who have antiphospholipid antibodies and may reduce the risk of heart attack and stroke.

Antidepressants Anti-depressant medications are used to treat depression and anxiety, present in almost half of all people who have lupus. You must speak with your doctor if you feel you are experiencing clinical depression because many people who are physically ill respond well to anti-depressant medications. In addition, your doctor may treat your depression in different ways depending on the cause.

Antiplatelet Medications (Platelet Antagonists) Some lupus patients are at an increased risk for blood clots due to the prevalence of a condition known as antiphospholipid antibody syndrome (APS). Platelet antagonists help prevent these clots and in doing so, also help to prevent heart attack, stroke, and other complications.

Osteoporosis Medications (Bisphosphonates) Bisphosphonates are medications used to treat and prevent osteoporosis. People with lupus are at an increased risk for this condition due to the inflammation they experience with the disease. Certain medications taken by lupus patients also increase the risk of osteoporosis, especially corticosteroids such as prednisone.

Blood Pressure Medications (Anti-hypertensives) 25-30% of people with lupus experience hypertension (high blood pressure). The most common causes of high blood pressure in people with lupus are kidney disease and long-term steroid use. Other medications, such as cyclosporine (Neoral, Sandimmune, Gengraf) can also cause elevations in blood pressure. It is important to remember that while diet and exercise are essential for optimal cardiovascular health, these elements alone may be insufficient in controlling your blood pressure; in this case, your doctor will prescribe a medication.

Anticoagulants Anticoagulants (“blood thinners”) are medications that decrease the ability of the blood to clot and are used in lupus patients with antiphospholipid antibodies to reduce the risk of deep venous thrombosis (DVT), stroke, and heart attack.

Gastrointestinal Medications Many people with lupus suffer from gastrointestinal problems, especially heartburn caused by gastroesophageal reflux disease (GERD). Peptic ulcers can also occur, often due to certain medications used in lupus treatment, including NSAIDs and steroids. Certain medications may be prescribed or recommended by your doctor to control these conditions.

Cholesterol Medications (Statins) Statins are medications that lower the level of cholesterol in your blood by reducing the production of cholesterol in the liver. People with high levels of cholesterol in their blood face an increased risk of cardiovascular disease, which can lead to chest pain, heart attack, stroke, and peripheral vascular disease. Studies have shown that people with lupus are more likely to have clogged arteries that can lead to heart attack and stroke at a younger age. This increased risk is caused by elevated cholesterol levels, high blood pressure, diabetes, and inflammation, conditions that occur often in people with lupus. Certain medications, such as corticosteroids (e.g., prednisone) can provoke or compound these symptoms. For this reason, the cholesterol-lowering properties of statins are commonly called upon for lupus patients.

Thyroid Medications Autoimmune thyroid disease is common in lupus. It is believed that about 6% of people with lupus have hypothyroidism (underactive thyroid) and about 2% have hyperthyroidism (overactive thyroid). A thyroid gland that is functioning improperly can affect the function of organs such as the brain, heart, kidneys, liver, and skin. Hypothyroidism can cause weight gain, fatigue, depression, moodiness, and dry hair and skin. Hyperthyroidism can cause weight loss, heart palpitations, tremors, and heat intolerance, and eventually lead to osteoporosis. Treatment for both underactive and overactive thyroid involves getting your body’s metabolism back to normal.

Fibromyalgia Medications Fibromyalgia is a chronic disorder characterized by widespread pain and tenderness, general fatigue, and non-restful sleep. Many people with lupus have fibromyalgia; in fact, much of the pain that people with lupus feel is due to this condition. Three medications are used to reduce some of the physical and emotional symptoms of fibromyalgia.

Restasis (Dry Eye Medication) Restasis is an immunosuppressive medication used to treat eye symptoms related to Sjogren’s syndrome, a chronic autoimmune disorder in which the glands that produce tears and saliva do not function correctly.