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The genetic signal controlling the blood-brain barrier was discovered

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The genetic signal controlling the blood-brain barrier was discovered

The genetic signal controlling the blood-brain barrier was discovered. In a new study, researchers have succeeded in identifying a genetic signal that controls the blood-brain barrier.

The genetic signal controlling the blood-brain barrier was discovered

New research in mice and zebrafish has discovered the genetic signal needed to form and maintain the blood-brain barrier.

The discovery could allow scientists to control the permeability of the blood-brain barrier and provide a more effective way to deliver drugs to the brain to treat stroke, neurological and psychiatric diseases, and cancer.

The blood-brain barrier (BBB) is a highly interconnected system of specialized cells that form a layered, semipermeable membrane that serves a dual purpose: protecting against toxins or pathogens entering the brain from the bloodstream while allowing passage through itself. gives vital nutrients.

Read More: The relationship between schizophrenia and mother’s vitamin D!

The blood-brain barrier is the separating area between the extracellular fluid of the brain in the central nervous system and the circulating blood flow in the body so that if colored substances are injected into the blood, it can be seen that there is no trace of this substance inside the brain. This curtain or barrier is made up of special capillaries, which, unlike the normal structure of capillaries, do not have the usual pores, and the intercellular connection in them is tight, and as a result, many molecules and micromolecules, as well as bacteria, are able to pass through them (through Diffusion) and reaching the cerebrospinal fluid is not in the brain. Conversely, the endothelial surface of these capillaries is covered with special proteins that allow glucose to enter the brain as nutrition. Also, gas exchange (oxygen-carbon dioxide) between circulating blood and the brain can be done without any problem through this barrier.

But the protective function of the blood-brain barrier can prevent effective drugs from being delivered to the brain to treat cancer, stroke, or neurological diseases such as Parkinson’s or Alzheimer’s.

Over the years, various methods have been developed to increase the permeability or leakiness of the blood-blood barrier to enable the delivery of drug therapies, including the use of magnetic nanoparticles, ultrasound, and engineered fat cells.

Now, a new study by Harvard Medical School researchers has identified a gene that produces a signal necessary for the development and maintenance of the blood-brain barrier and may provide a way to control its permeability.

Researchers have long known that the permeability of the blood-brain barrier is controlled by surrounding cells, but the genes in those cells remain unknown. Of course, when the researchers in the current study began to investigate the blood-brain barrier in zebrafish, the answers to these questions became clear.

In previous studies on transparent zebrafish, researchers discovered a gene called mfsd2aa that, when mutated, caused the blood-brain barrier to leak throughout the brain. But in some zebrafish, this barrier was permeable only in the forebrain and midbrain, not in the hindbrain.

“This observation led me to find a gene that makes the blood-brain barrier more permeable,” says Natasha O’Brown, lead author of the study.

In the present study, the researchers conducted additional experiments on zebrafish and mice. They found that region-specific breakdown of the blood-brain barrier is associated with mutations in the spock1 gene, which is expressed in nerve cells throughout the retina, brain, and spinal cord, but not in cells that form the blood-brain barrier.

They observed that spock1 mutant animals had more vesicles in their endothelial cells, which are key components of the blood-brain barrier. Vesicles are bubble-like membranes that store and transport cellular products and can transport large molecules across the blood-brain barrier. They also have a smaller basement membrane, which is a network of proteins found between endothelial cells and pericytes, cells that are important for forming blood vessels and maintaining the blood-brain barrier.

RNA analysis showed that spock1 alters gene expression in endothelial cells and pericytes in the blood-brain barrier, but not in other brain cell types.

When the human Spock1 protein was injected into the zebrafish brain, the endothelial cells and pericytes were repaired at the molecular level and restored about 50% of the blood-brain barrier function.

Based on this discovery, the researchers concluded that the Spock1 protein produced by neurons begins to form the blood-brain barrier during embryonic development and helps maintain it during adulthood.

“Spock1 is a potent secreted neurosignal that can promote and induce barrier properties in these blood vessels,” says O’Brown. Without it, you don’t have a functional blood-brain barrier.

The researchers say their study provides a more complete picture of the permeability of the blood-brain barrier and opens the door to the development of therapies that target spock1, potentially improving the treatment of neurological disorders such as Parkinson’s and Alzheimer’s and psychiatric disorders.

This is not the first neural signal that scientists have found, but it is the first signal from neurons that appears to specifically regulate inhibitory properties, Oberon says. I think this discovery gives us a powerful tool to try and change.

The researchers continue to look at how different pericytes are affected by spoc1 signaling. They would like to see if administering spock1 can counteract the effects of stroke on the blood-brain barrier.

This study was published in the journal Developmental Cell.

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Discovery of the brain circuit that manages inflammation

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Researchers believe that using this new brain circuit could lead to new treatments for many immune disorders.

Discovery of the brain super circuit that manages inflammation

Researchers have found that brainstem neurons act as regulators of inflammation. These neurons can increase or decrease inflammation in response to signals sent by the vagus nerve, a collection of thousands of nerve fibers that connect the brain and internal organs.

A new study in mice shows that a peripheral immune stimulus powerfully activates the body-brain axis to regulate immune responses, according to AI. Pro- and anti-inflammatory cytokines communicate with specific populations of vagal neurons to inform the brain of an emerging inflammatory response. The brain, in turn, strongly modulates this environmental immune response process.

Cytokines are a group of water-soluble protein molecules that are secreted from various cells in response to a stimulus and are responsible for transmitting messages between cells. The consequence of the presence of cytokines is a change in the behavior of cells with secreted cytokine receptors, including growth, change, or cell death. The action and effect of cytokine produced by one cell includes more cells around the same cell, but it can have a systemic action and effect on the whole organism.

Cytokine has the effect of changing the secreting cell itself and changes in other cells, and like a hormone, it can have effects on cells far away from it.

The vagus nerve is also the longest brain nerve and the tenth pair of brain nerves out of 12 pairs of brain nerves, which is involved in swallowing food, speaking, parasympathetic activities, and digestion. The motor part of this nerve is somatic and innervates the larynx, soft palate, and pharynx. This nerve is the longest cranial nerve, and like most cranial nerves, it starts from the brain stem and is divided into many branches that innervate most of the muscles of the pharynx and larynx, esophagus, stomach, and parasympathetic heart, lung, liver, spleen, etc.

Discovery of the neuro-immune axis

Based on this study, the researchers used single-cell RNA sequencing, combined with functional imaging, to identify circuit components of this neuro-immune axis and show that its selective manipulation can effectively suppress the pro-inflammatory response while maintaining an anti-inflammatory state. 

This new brain circuit, like a thermostat, helps increase or decrease inflammatory responses so the body responds in a healthy way, said Dr. Hao Jin, who began the study as a postdoctoral researcher in Dr. Zucker’s lab.

Looking at past research, it makes sense that a master regulator controls this critical response, the researchers say. Many psychosomatic effects can actually be related to brain circuits that tell your body something.

They believe that using this new brain circuit could lead to new treatments for many immune disorders.

Promising therapeutic potential

Brain-induced transformation of an immune response pathway offers new possibilities in modulating a wide range of immune disorders, from autoimmune diseases to cytokine shock.

“This new discovery could open up an exciting therapeutic area for controlling inflammation and immunity,” said Charles Zucker, senior author of the study.

Researchers believe that controlling this newly discovered brain circuit could lead to new treatments for common autoimmune diseases including rheumatoid arthritis, type 1 diabetes, multiple sclerosis, lupus, and inflammatory bowel disease.

Read more: Brain cancer vaccine success in human trials

This new control agent could also help treat other diseases such as prolonged COVID-19 syndrome, organ transplant rejection, and cytokine storms caused by COVID-19. According to the researchers, inhibiting the activity of this circuit could make a difference in a wide range of conditions that affect the immune system and help treat dysregulated inflammatory states in people suffering from diseases and immune disorders. This study was published in the journal Nature.

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Skin cancer: symptoms, prevention and treatment

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Skin cancer is the most common cancer in Iran. Do you know enough about this disease?

Skin cancer: symptoms, prevention and treatment

Skin cancer is the abnormal growth of skin cells. This problem generally occurs in areas of the skin that are exposed to sunlight, but sometimes it occurs in areas of the skin that are not normally exposed to light.

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The strange ways skin affects our health

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Skin not only reflects our lifestyle but also plays an active role in our physical health and is related to various diseases.

The strange ways skin affects our health

Worn-out or unhealthy skin is a major contributor to every age-related disease, from Parkinson’s to type 2 diabetes. BBC journalist Zarya Gorot explains how skin affects health and how to protect it.

I am boating in the Ardèche Strait in the south of France when I notice people’s strange looks. It is early afternoon on a scorching July day and the sky is blue and clear. Although there are high cliffs on both sides of the river, I have never felt the sun’s rays so strongly.

The sun’s rays have turned the surface of the water into a squiggly path of brilliant light that is impossible to look at. I have chosen my outfit with the seriousness of an explorer who is going to walk in the African desert. My clothes cover my whole body and protect me from the sun. I used a wide-brimmed fishing hat as well as plenty of high SPF sunscreen and I didn’t forget my sunglasses. I am determined to prevent further aging from the sun. But are there other hidden benefits to these extreme measures of mine?

The latest research shows that our skin is not just a mirror of our lifestyle that reflects the effects of years of smoking, drinking alcohol, and stress. According to the new view, the skin as the largest organ of the body is an active participant in our physical health, and wrinkled and dry skin itself causes aging.

Weird theory

In 1958, the Baltimore Longitudinal Study began, which was supposed to be a scientific study of aging with a bold and rather unorthodox hypothesis. Before that, scientists used to study donated cadavers to understand the physiology of living people. But this time the subjects were examined while their hearts were still beating and their bodies were fully alive. Researchers have followed thousands of men and women for decades to study how genes and environment affect their health.

Wrinkled and dry skin causes aging

In the two decades since the Baltimore study began, scientists have made interesting advances: from the discovery that men who were emotionally unstable were more likely to develop heart disease to the discovery that our problem-solving abilities decline slightly as we age. .

One of the most striking findings of the Baltimore study confirms what researchers have long suspected: how young you look is an accurate measure of how healthy you are inside. In 1982, researchers found that men who looked much older than their age at the start of the study were more likely to die.

In more recent studies, 99% of patients who looked at least 10 years older than their actual age had health problems. It appears that skin health can be used to predict a number of seemingly unrelated factors, from bone density to the risk of developing neurodegenerative diseases or death from cardiovascular disease. But is the skin merely a sign of damage that has accumulated in us, or is it something more complex: can it preserve the health of the healthy and worsen the condition of the unhealthy?

Chronological age and biological age

There are two main ways to measure people’s age. The first method is the standard method known as chronological age. But there is also biological age, which shows the speed of aging of the body. Biological age may vary between different people and even within the same body.

As we age, our chronological age eventually affects our appearance: skin becomes thinner and more uneven, and its elasticity decreases; Because the cells responsible for the production of pigment and collagen die or get old. But usually, the environment causes real damage to the skin.

Although UVB rays can damage our DNA and cause sunburns, mutations, and skin cancer, 95% of all UV radiation reaching the Earth’s surface is UVA. This part of the sun’s rays has a longer wavelength and can penetrate deep into the skin, break down collagen, and stimulate cells to produce melanin.

At the microscopic level, skin that has aged due to exposure to sunlight is thicker and has malformed collagen and elastin fibers. On the visible surface, such skin has an uneven color and is significantly more wrinkled.

Even the darkest skin can burn and is susceptible to photoaging, although it takes longer for wrinkles to appear.

SkinWhile UVB rays usually damage the surface of the skin, UVA penetrates deep into the skin and both can cause systemic inflammation.

Internal factors are thought to be responsible for a small part of skin aging, while UV light is responsible for more than 80% of visible skin changes.

Along with the physical effects described, the skin also undergoes a chemical transformation, and this is something that may have a profound effect on our general health.

Inflammatory aging

In 2000, a group of scientists from the University of Bologna in Italy proposed a new way of thinking about aging by observing how organisms react to stress.

In a healthy young person, the immune system normally functions to maintain order, that is, to repair damage and fight off infections. But when we age or when our health is not good, these inflammatory responses can cross a certain threshold and trigger the release of a cascade of powerful chemicals that travel throughout the body, destroying healthy cells and breaking DNA.

Even the darkest skin is susceptible to sun aging and can burn

The term inflammatory aging is used to describe the global inflammation that accompanies the aging process. Research shows that wrinkled, diseased, or damaged skin becomes part of the inflammatory system and releases chemicals that cause further damage and inflammation.

Higher levels of inflammatory cytokines and chemokines are observed in aged skin. These chemicals destroy collagen and elastin and cause thinning, wrinkling, and loss of skin elasticity. They also disrupt the skin barrier, increasing water loss and susceptibility to stressors. This feedback loop combines with aging cells in the skin, which in turn release their own inflammatory chemicals. Chemicals released by unhealthy skin enter the bloodstream and from there reach different tissues and damage them. The result of this is accelerated aging and a higher risk of various diseases.

So far, old or diseased skin has been associated with the onset of cardiovascular disease, type 2 diabetes and cognitive disorders, as well as Alzheimer’s and Parkinson’s disease.

The importance of skin protection

The first step to protecting your skin is to avoid the sun. In order to protect the skin, observe the following:

  • Wear protective clothing against sunlight.
  • Use sunscreen with a high protection factor.
  • Wear a brimmed hat.
  • Use sunglasses.
  • Do not stay in the sun as much as possible.

Protecting the skin from the sun is very effective in preventing the visible signs of aging. In a preliminary study, those who used a broad-spectrum sunscreen with an SPF of 15 every day for four and a half years showed no signs of further skin aging.

Rubbing the cream on the skinMoisturizing the skin reduces inflammation.

The important thing in choosing a sunscreen is to choose a product that is broad-spectrum. Broad-spectrum sunscreen not only absorbs or reflects UVB (indicated by SPF) but also protects against UVA. Dermatologists recommend that you always check the product label for UVA protection. Protection against UVA is usually indicated by UV-PF or PPD.

Sunscreen can prevent inflammation that occurs when the skin is exposed to the sun, and as previously mentioned, inflammation is the first step toward aging-related diseases. But using sunscreen is not the only way to maintain skin health.

The easiest way to improve skin health is to moisturize it. Moisturizing the skin reduces inflammation and may even help prevent dementia.

In addition to uneven color and wrinkling, skin that has aged due to exposure to sunlight and age is drier. The moisture level of human skin reaches its peak at the age of 40, and after that, it decreases drastically and produces less amounts of natural moisturizers, namely lipids, filaggrin, sebum, and glycerol.

Dry skin is problematic because when the skin is dry, its function as a barrier between the inside and the outside of the body is weakened. When our skin is dry and scaly, its natural functions (keeping out infectious agents, environmental toxins, and allergens while maintaining moisture) become more difficult.

Sunburn of the skinSun-damaged skin releases chemicals that contribute to systemic inflammation and increase the risk of age-related diseases.

Adding moisture to the skin is not a complicated task, and this simple intervention produces significant results.

A group of researchers asked elderly volunteers to use a topical moisturizer twice a day for a month. Compared to older participants who did not use moisturizer, their skin was significantly repaired and their skin levels of inflammatory chemicals were lower.

Even the simplest moisturizers can help prevent inflammatory aging

The promising results of the above study were followed by another study in which people over the age of 65 used a moisturizing cream twice a day for three years. The cognitive performance of the participants was measured at the beginning and at the end of the study. After three years, the cognitive performance of the participants in the control group had declined significantly, but the cognitive performance of the group that hydrated their skin had not.

Read more: Inventing a new drug to treat influenza

Dry skin usually has a higher level of inflammation and is often itchy. A decrease in the level of hydration of the stratum corneum (the outer layer of the epidermis) probably plays a major role in inflammatory aging. On the other hand, scratching the skin intensifies the inflammation.

Natural ingredients include glycerol, petroleum, hyaluronic acid, and lipids that are normally found in the outer layer of the skin and are also the natural components of the most basic moisturizers. Drinking more water may also help hydrate the skin, although the evidence is unclear.

To visualize how much skin can affect the rest of your body, think about how much skin you have. There is as much skin on the inside of your body as there is on the outside of your body. When skin is damaged, every inch of it can release toxic chemicals. Therefore, protecting the skin from the sun is a very effective solution, but don’t forget to use moisturizer as well.

Conclusion

The skin not only indicates the internal state of our body and our lifestyle but also plays a role in age-related diseases. When the skin is exposed to environmental factors, especially sunlight, in addition to changes in appearance, it undergoes chemical changes and contributes to various diseases by participating in global inflammation.

Use a broad-spectrum sunscreen to protect your skin from the sun. Using a moisturizer also helps prevent and reduce inflammation and prevent skin damage.

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