Skin Cells Can Transform To Help Fight Acne

When acne-causing bacteria strike, the immune system can fight back by transforming some of the surrounding cells into fat cells that emit antimicrobials, finds a study published February 16 in Science Translational Medicine. The scientists behind the project say the revelation could lead to new, targeted treatments.

Cutibacterium acnes typically causes pimples after it infects a hair follicle, feasts on trapped debris, and triggers inflammation by releasing digestive enzymes that damage nearby cells. However, the researchers discovered that C. acnes infections can trigger adipogenesis—the transformation of cells into fat cells, or adipocytes—in skin cells called fibroblasts surrounding an infected hair follicle. While the lipids these cells begin to store can aid the development of lesions—or more colloquially, pimples—the data also suggest that adipogenesis triggers increased expression of the gene CAMP, which codes for an antimicrobial peptide called cathelicidin that helps curb the bacterial infection.

The finding that fibroblasts transform to play an active role in the immune response came as a surprise to Salome Muravvej, a dermatologist in Mombasa, Kenya, who didn’t work on the study. She tells The Scientist over email that “the fibroblasts are mainly viewed as the cell that provides structural support, especially for deeper layers of skin, so it’s not the first cell type that would come to mind when thinking of directly fighting skin infections.”

The research team, led by University of California, San Diego, dermatologist Richard Gallo, also learned that retinoids—already used as a treatment for severe acne because of their well-known ability to prevent lipid buildup and clear detritus from infected pores—also promote the fibroblasts’ production of cathelicidin, hinting at the prospect of developing new treatments that specifically target and enhance the immune response to acne.

“The prevailing theory about the action of systemic retinoids like isotretinoin (Accutane) has been that it worked by decreasing lipid synthesis from sebaceous glands and altering the growth of the epidermal cells,” Gallo tells The Scientist in an email. “Our data suggest that is not the whole story.”

Artist’s depiction of acne formation

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Study coauthor Alan O’Neill, a microbiologist in Gallo’s lab, tells The Scientist that the paper “provides a new mechanism of action for a very important drug in the treatment of acne. This drug is working in an additional, previously unknown way by targeting these fibroblasts, and specifically targeting their pathogenic antimicrobial expression.”

“It was a very interesting and surprising finding,” Muravvej says. She adds that it’s “also a reasonable finding,” because “reactive adipogenesis has been shown by prior studies to occur in response to Staphylococcus aureus invading skin, and also in the gut in response to injury (to suppress penetration of microbial products into the bloodstream.)”

Pimple probes

To determine how fibroblasts respond to C. acnes infections, the researchers biopsied skin samples from six acne patients and probed the fibroblast transcriptome with single-cell RNA sequencing. They found that two subsets of fibroblasts had gene expression signatures indicating they were primed for fat cell differentiation—as Gallo tells The Scientist, they had become “preadipocytes.” The researchers also stained the skin samples to search for a marker called PREF1, which is expressed in fibroblasts undergoing adipogenesis, in addition to cathelicidin. They found high levels of both in the tissue surrounding infected hair follicles, indicating a localized immune response.

The team then recreated the experiment in a mouse model, injecting mice with C. acnes and conducting a nearly identical RNA sequencing experiment on biopsied skin lesion tissue. The researchers found increased staining for PREF1 and the antimicrobial peptide coded for by CRAMP, the mouse version of CAMP, in the cells closest to the lesion. When they inhibited reactive adipogenesis by treating mice with bisphenol A dyglycidyl, the researchers found significantly less lipid buildup—and significantly smaller lesions—than in a control group, suggesting that the lipid buildup that comes with adipogenesis benefits the bacteria, even in the presence of increased antimicrobial activity.

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“The animal model was really powerful because essentially it validated a lot of the work that we did in human acne,” O’Neill tells The Scientist, with very similar findings. Gallo says that the animal model was “critical.”

“Human acne is very complicated,” he says. “It’s a multifactorial disease. But the fact that we saw similar transcriptional programs in mice that were injected with just a single [species of] bacteria—that was really strong and that told us that the bacteria C. acnes is probably what’s driving a lot of this reaction in fibroblasts in human acne.”

The team then probed how mouse cells communicated with each other during C. acnes infections, analyzing how cells and surface proteins interacted to identify active signaling pathways. They found that the fibroblasts served as communication hubs, according to the paper, and O’Neill suggests that these cells play an important role in coordinating the immune response to C. acnes infection and acne development.

“We would love to know how macrophages, myeloid cells, and other immune cells respond to these fibroblasts that are undergoing reactive adipogenesis, and what that means for the overall inflammatory environment of acne,” O’Neill tells The Scientist, adding that he hopes to conduct experiments designed to map out those relationships in the near future.

Testing treatments

Gallo, O’Neill, and the rest of the team also wanted to know how retinoids, a class of compounds that’s been used to prevent and treat severe acne for more than 50 years, affect reactive adipogenesis. They began by treating mice with retinoic acid on day three after an initial C. acnes infection. Three days after that, the researchers observed reduced lesion size and severity that coincided with increased CAMP mRNA expression and reduced lipid staining, according to the paper.

See “Skin Microbes Help Clear Infection”

However, when they recreated the experiment on mice that had been gene-edited to disable their CRAMP genes, the researchers found that retinoids seemed to have no effect. The mice had larger lesions than wild-type mice even though lipid formation in adipocytes was inhibited. Gallo explains that the team noticed a change in how the mouse model responded to the bacteria after they performed the targeted deletion of the peptide—evidence of a link between the peptide and the immune response to C. acnes infection.

That last discovery serves to put together pieces first hinted at in a study that Gallo and his colleagues published in The Journal of Immunology in 2019, which demonstrated increased cathelicidin expression after retinoid treatment, to now reveal that retinoids treat and prevent acne in part by influencing the behavior and function of fibroblasts. Specifically, they inhibited lipid generation among fibroblasts undergoing adipogenesis without preventing the increased expression of adipogenesis-related antimicrobial peptides—a previously undiscovered therapeutic mechanism.

The study, Gallo tells The Scientist, “suggests that we have overlooked an important target to treat acne. ”

These new findings are clinically interesting, Muravvej tells The Scientist, because they broaden the anatomical region that might be relevant to acne treatment. Typically, she explains, clinicians and researchers focus specifically on an infected hair follicle, which she calls “the primary anatomical site for acne,” and don’t examine the surrounding tissue implicated in the new study.

Mark Blaskovich, an infectious diseases researcher at the University of Queensland who didn’t work on the study, tells The Scientist that there “aren’t any direct potential therapeutic outcomes” of this paper, “just more of an understanding about why existing retinoid therapy may work.” However, he adds that retinoids can cause severe side effects, including impairing fetal development, so “improving our fundamental understanding may lead to ideas [for] how to target these pathways to come up with alternative treatments.”

‘Clear Head’ – With Elite Team Behind Her, Amber Kitchen Ready For Breakout Performance At ONE Fight Night 11

Despite not getting the results she’s chased in ONE Championship so far, Amber Kitchen feels more confident than ever ahead of her return on Friday, June 9.  

The 24-year-old English striker passed on the reins of her gym and moved to the opposite end of the country to focus strictly on her training, and she thinks that sacrifice will pay dividends when she faces Martine Michieletto at ONE Fight Night 11: Eersel vs. Menshikov on Prime Video. 

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Kitchen had taken over head coaching duties at her family’s academy, Touchgloves Gym, in Cornwall and split her time training with fellow ONE star Liam Harrison at Bad Company in Leeds last year. But after falling to Diandra Martin in her most recent battle last August, “AK 47” decided to relocate and fully devote herself to perfecting her craft.

Now, in the days leading up to ONE Fight Night 11, Kitchen believes she will be more prepared physically and mentally when she steps into the ring for her strawweight Muay Thai battle at Lumpinee Boxing Stadium in Bangkok, Thailand.

She said:

“I’ve moved to Bad Company permanently now. I’m just feeling amazing for this one. Everything’s going perfectly to plan.

“I’ve got no distractions of running my own business down in Cornwall anymore. And I’ve come away from my whole life just to dedicate it to this fight. It’s a good feeling. Clear head. 

“I’m feeling super confident because I had such a long camp. In my last camp, I had six weeks’ notice, but for this one, I’ve had 12. I couldn’t have asked for anything better.”

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Kitchen has come up short in three competitive matches during her promotional run, and she could be forgiven for feeling deflated. But with a new camp supporting her, she knows the results will come.

The British striker has taken away plenty of positives from her previous outings and has sharpened her skills over the past several months. And on June 9, she hopes it will translate into a much sought-after victory on the global stage.

She offered:

“I’ve taken on the top opponents in the division. I know I’ve had losses, but I’m putting on exciting performances. They’re not one-sided. I’m still standing there and giving as much as I take.

“I really, really want to win in ONE, and especially on these Lumpinee cards. All the cards are amazing, but the Lumpinee cards are so fiery. I just really want to do Bad Company proud in this one. They’ve put so much time and effort into me.”

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Amber Kitchen’s next opponent is Martine Michieletto – an ISKA Kickboxing World Champion who will step onto the global stage for the first time in Bangkok.  

“The Italian Queen” brings a strong resume with her to the big leagues, and she certainly has the English star’s respect. But “AK 47” believes her athleticism, as well as her familiarity with the Global Muay Thai Rule Set and experience competing on such a massive stage, puts the bout in her favor.

Kitchen said:

“Anyone who is in ONE is obviously very talented and high-level, so I can’t knock anyone, but I feel confident going into this fight – not from watching her, but just from the amount of training that I’m doing. I know she’s not training as hard as I am. I’m training three to four times a day. 

“I’ve watched some of her videos, and the speed is there, but I don’t feel like she’s got much power. I feel like she’s going to come out all guns blazing. She’s very explosive. But I don’t know how long she can keep that up, especially not when she’s being hit in the four-ounce gloves and being on such a big platform. I feel like I’ve got that advantage on her. ”

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Kitchen also feels like she has the edge in the power stakes, and there’d be no better way to enter the win column than with an emphatic stoppage. 

The Brit’s losses have been in games of inches, and she has zoned in on the small details that can convert narrow defeats into victory.

“AK 47” explained:

“I’ve been working a lot on getting my distance right. I feel like I’ve got knockout power. I just haven’t had that accuracy with the distance so far. So, I’ve been working a lot on that. 

“I want to go and do some damage on her. I feel like I can knock her out.”

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Scientists make a breakthrough in the fight against Alzheimer’s

October 10, 2013

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Scientists hope to stop the death of affected brain cells

The British Medical Research Council has unveiled a chemical compound that can fight Alzheimer’s and several other neurodegenerative diseases.

Experts have already called it a “breakthrough” in medicine.

However, there is still a long way to go to develop drugs that patients can take.

The scientists say that the resulting compound in the future will be able to seriously help primarily those suffering from Alzheimer’s, Parkinson’s, Huntington’s disease (also known as “St. Vitt’s dance”) and other diseases of the nervous system.

Tests on mice have shown that the death of brain cells from currently incurable diseases of the nervous tissue can be prevented by using the found substance, reports the British Medical Research Council.

“It looks like this study will go down in history as a turning point in the fight against Alzheimer’s. I’m very impressed,” Professor Roger Morris of King’s College London told the BBC.

According to him, this is the first proof that neurodegeneration can be stopped.

“The world will not change tomorrow, but this is a scientific breakthrough,” the scientist believes.

Starving cells

Researchers from the Department of Toxicology at the University of Leicester have focused on the brain’s natural defense mechanisms.

When a virus “hacks” a cell, the process of producing viral proteins begins. In the cell itself, the process of producing proteins is practically stopped in order to stop the spread of the virus. As a result, cells die because they stop producing “healthy” proteins and “starve”.

This process is repeated in the mass of neurons in the brain. As a result, the patient’s memory is sharply weakened, he may die.

Such “cracking” of the cell structure is considered to be the cause of a number of diseases. Its safe interruption can cure the sick.

A study published in the journal Science Translational Medicine notes that mice with neurodegenerative diseases quickly lost their memory and died within 12 weeks.

However, in rodents given the new compound, brain tissue did not die.

“They were fine, it’s amazing! I was particularly delighted that the compound completely prevented the destruction of neural tissue. It’s not something we can treat patients with yet, but it’s a start,” researcher Giovanna Mallucci told the BBC.

According to the scientist, a new chemical compound paves the way for the creation of a full-fledged pharmaceutical drug that could be used by people.

“Impressive results”

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Prof. Mallucci’s laboratory is also testing the substance on mice with other forms of nerve tissue disorders, but the results of these tests have not yet been published.

Researchers, of course, do not forget about side effects.

Rodents healed of neurodegenerative disease began to suffer from pancreatic problems, lose weight and acquire diabetes.

Scientists emphasize that the finished drug should only affect the brain. Nevertheless, the basis for working on the drug has already been created.

Lancaster University neuroscience specialist David Allsop called the results “impressive and very encouraging,” but noted that more research would be needed for accurate results.

“By tackling the mechanism that triggers neurodegenerative diseases, we could have one drug that could benefit a wide range of diseases. However, this compound is still in its early stages of development,” says Dr. Eric Katran of Alzheimer’s Research UK.

“It is important that these studies be repeated and that models of other diseases be tested, including Alzheimer’s disease,” says the specialist.

Vaccine against brain cancer: a revolutionary breakthrough or a new step in the fight against the disease

The news about the trials of a vaccine against brain cancer sounded fantastic – is it really possible to get “vaccinated” against a terrible disease? Medical journalist Yelizaveta Babitskaya explains what the essence of the new development is and why victory over cancer is still far away. For a person who is far from medicine, this may sound revolutionary, but in fact it is only a step in the treatment of gliomas. This does not mean that the vaccine is capable of preventing the development of this type of cancer in humans, as it might seem at first glance. Will we ever have vaccines to cure cancer? Medical journalist Elizaveta Babitskaya answers.

Vaccines that reduce risk

Vaccines are medicines that help the body fight disease. They allow you to train the immune system so that it quickly detects and destroys dangerous viruses and bacteria. The situation is similar with cancer vaccines. Among them, a group of drugs can be distinguished that can reduce the risk of developing certain cancers in humans. The fact is that certain types of cancer can appear due to viral diseases. If they are not in the body, the likelihood of getting sick is greatly reduced.

These vaccines now include hepatitis B and human papillomavirus (HPV). The first, according to the recommendations, is done to children in the first days of life. It helps to protect a person from the reproduction of the hepatitis B virus in the body: thanks to this, he will not develop a chronic form of hepatitis, which causes constant inflammation in the liver, which sometimes eventually leads to cirrhosis and cancer.

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The HPV vaccine is still more interesting. As it turned out, certain types of this virus, which are called highly oncogenic, are almost always to blame for the development of cervical cancer. They insert their DNA into cells, which causes them to malfunction and can lead to malignant tumors. In addition to cervical cancer, HPV has also been linked to cancers of the vagina, vulva, anal canal, oropharynx, and penis. HPV is a virus that is most commonly transmitted sexually. Therefore, children (both boys and girls) are advised to vaccinate before the onset of sexual life, until they encounter it. According to the recommendations of the World Health Organization, this should be done in the period from 9up to 14 years old. A new study from Sweden shows that HPV vaccination can reduce the risk of developing cervical cancer by up to 88% (if girls are vaccinated before the age of 17). If we add to this a high-quality screening system – early detection of cervical cancer, then the world has every chance to deal with this disease almost completely.

But even such vaccines do not guarantee an individual a 100% cure for cancer in the future. Liver cancer can appear not only because of hepatitis B, but also, for example, because of severe alcohol dependence. HPV vaccines do not protect against absolutely all highly oncogenic types of HPV, but only against those that most often lead to cervical cancer, which means that the risk still exists.

Vaccines that cure

In addition to vaccines that help people fight individual cancer-causing viruses, there are so-called therapeutic vaccines. These include the new development of German scientists. These drugs are aimed at treating pre-existing tumors and are classified as immunotherapy. With this type of treatment, doctors try to direct the work of the person’s own immune system against cancerous tumors.

On the surface or inside of cancer cells, certain antigens can often be found that other cells in the body do not have. On this “hook” cells of the immune system can recognize and begin to attack the tumor. Therefore, some cancer vaccines are made up of cancer cells, parts of cells, or pure antigens. This helps to “start” the body’s rapid immune response.

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There are different options to create a vaccine. Sometimes the patient’s own immune cells are taken from the patient and a personal vaccine is prepared on their basis. It can only be used for one person. These drugs include a vaccine to treat prostate cancer that does not respond to hormone therapy. But there are also “public” vaccines, such as Talimogene laherparepvec (T-VEC), which is aimed at treating severe stages of melanoma.

Some other vaccines can simply stimulate immunity in a specific area. These include BCG, familiar to everyone, with the help of which children are vaccinated against tuberculosis. It turned out that it also works for the treatment of bladder cancer. If it is injected directly into this organ, it can prevent the growth of cancer and its reappearance.

How the brain tumor vaccine works

Does this mean that scientists have already learned how to effectively treat brain tumors with vaccines? Alas, it’s too early to talk about it. But it seems that researchers from Germany are on the right track. Their invention is also a therapeutic vaccine, in fact, a drug that can be used to treat cancer that has already appeared. They were able to take advantage of the fact that some types of gliomas often have a mutation in the isocitrate dehydrogenase-1 (IDh2) gene. This made it possible to create a vaccine that can call on individual cells of the immune system – T-helpers – against such tumors.

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The drug has already been studied in humanized mice, which showed its promise, and the first phase of clinical trials in humans has recently ended. It involved 33 patients with newly diagnosed grade 3 and 4 gliomas who had an IDh2 mutation. During the study, people both received standard therapy (chemotherapy or radiation therapy) and were vaccinated with a new drug. As a result, it was shown that the immune system of people reacts to the vaccine, and the drug does not cause serious side effects, which means that it is safe to use. At this stage, nothing can be said about the effectiveness of such treatment, this will be studied in the next phases of the clinical trial. What result the scientists will get in the end is not yet clear, but let’s hope for the best: the vaccine will show its effectiveness in the treatment of gliomas, and we will have another way to prolong the lives of people with this serious illness.

This is not a unique case – development of similar vaccines for different types of cancer and their clinical trials are now taking place in different parts of the world.