Scientists discover a dynamic cellular defense against breast cancer invasion

Johns Hopkins researchers report they have demonstrated in mouse tissue grown in the lab that the cell layer surrounding breast milk ducts reaches out to grab stray cancer cells to keep them from spreading through the body. The findings reveal that this cell layer, called the myoepithelium, is not a stationary barrier to cancer invasion, as scientists previously thought, but an active defense against breast cancer metastasis.

Results of the scientists’ experiments are published online July 30, 2018, in the Journal of Cell Biology.

“Understanding how cancer cells are contained could eventually help us develop ways to predict a person’s individualized risk of metastasis,” says Andrew Ewald, Ph.D., professor of cell biology at the Johns Hopkins University School of Medicine and a member of the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center.

Most breast tumors begin in the cells that line the interior of breast milk ducts. These cells in turn are surrounded by myoepithelial cells, Ewald says, which work together to contract and move milk through the ducts when a baby is nursing.

This myoepithelial layer is used clinically to distinguish contained breast cancers from invasive cancers in humans. When breast cancer cells breach the myoepithelial layer, the result is so-called invasive carcinoma, which is associated with higher rates of recurrence and the need for more aggressive treatment, says Ewald.

“If you think about metastasis as a long race, breaking through this layer is the exit from the starting gate,” says Ewald.

For their study, Ewald and his team engineered cells taken from the lining of mouse breast ducts to produce the protein Twist1, which works by altering gene expression and which has been linked to cancer metastasis in multiple tumor types.

To their surprise, the researchers saw that when the invasive Twist1 cells broke through the myoepithelial layer, the myoepithelial cells grabbed the cells that had gone astray and successfully pulled them back within the breast duct lining 92 percent of the time through 114 observations.

“These findings establish the novel concept of the myoepithelium as a dynamic barrier to cell escape, rather than acting as a stone wall as it was speculated before” says Katarina Sirka, a Ph.D. student from the Ewald laboratory.

To confirm that their findings were active behaviors, Ewald and his team altered two key characteristics of myoepithelial cells — their ability to contract and their numerical ratio to the invasive cells.

First, the researchers genetically engineered mouse myoepithelial cells to deplete their smooth muscle actin, a protein that allows the cells to contract. Under that condition, the number of escaped invasive cells that broke through the myoepithelial layer increased threefold compared to control cells with a normal myoepithelium.

Likewise, the researchers found that decreasing the proportion of myoepithelial cells to invasive cells increased the number of escaped cancer cells. By adding just two myoepithelial cells for each invasive cell, the escape rate decreased fourfold compared with the spread of invasive cells with no defending barrier.

“This is important to know because it suggests that both the physical completeness of the myoepithelium and the gene expression within the myoepithelial cells are important in predicting the behavior of human breast tumors. Anywhere this layer thins or buckles is an opportunity for cancer cells to escape,” says Eliah Shamir, M.D., Ph.D, who is currently a surgical pathology fellow at the University of California, San Francisco.

In the future, Ewald and his team plan to study the cellular mechanisms prompting the myoepithelial layer to react so dynamically and what makes it fail during invasive progression.

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Jenna Jameson Is Intermittent Fasting AND Doing Keto

jenna jameson keto intermittent fasting

Earlier this month, Jenna Jameson revealed a 57-pound weight loss on Instagram, noting that she attributes the body transformation to the keto diet.

Now, the former adult film star and mom of three took to Instagram again to share that she’s recently taken up intermittent fasting on the keto diet, too—and she says it’s working out for her.

As Jenna, 44, wrote in her recent post, it’s not uncommon for people on the keto diet to also work in some intermittent fasting:

“I absolutely was not sure about this,” she said. “Some keto peeps swear by it, others say it’s incredibly hard.”

Let’s talk #intermittentfasting 👏🏻 I absolutely was not sure about this. Some keto peeps Swear by it, others say it’s incredibly hard. So what it essentially is, is stopping eating at a certain time and restarting (usually) 16 hours to 18 hrs later. I figured this would be a great way to break the 130 lb plateau I hit. I’ve done it two days now, stopping at 6 pm and eating again at 11 am. This is absolutely doable for me. I’ve lost two pounds easily and am sitting at 127, so for you mamas out there that are feeling stalled out on your keto diet, this is something to try!!!! #ketocommunity #keto

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Jenna says she started intermittent fasting in order to break through her weight-loss plateau, adding that she typically fasts for a 16- to 18-hour period.

“I’ve done it two days now, stopping at 6 p.m. and eating again at 11 a.m.,” she says. “This is absolutely doable for me.”

Jenna’s particular brand of intermittent fasting plan sounds a lot like the 16:8 diet, which involves fasting for 16 hours a day, then eating whatever you want for the remaining eight hours.

A study published in the journal Nutrition and Healthy Aging showed that people did have success with modest weight loss using the plan and also lowered their blood pressure.

Experts say that pairing intermittent fasting with the keto diet might lead to more fat-burning (and weight loss) since both the keto diet and intermittent fasting help the body achieve ketosis, a.k.a. the state where your body burns fat for fuel instead of carbohydrates.

Beyond her weight loss, though, Jenna has also been vocal about how the keto diet has made her feel, saying that she is “happier, smarter, and much more confident” since starting the diet.

Thought I’d post a #motivationmonday #beforeandafter of my total weightloss. On the right I weight 187. On the left I’m a strong 130. I was lethargic and struggled with the easiest of tasks like walking in the beach sand with Batelli. 😞 I felt slow mentally and physically. I took the pic on the right for a body positive post I was going to do and decided against it because I felt anything but fucking positive. I’m now a little under 4 months on the #ketodiet and it’s not only given me physical results, I feel happier, smarter, and much more confident. I also want to let y’all know how much your amazing support means to me. I know you loved me heavy, and now… but your journeys inspire me to keep inspiring you. Thank you for going on this journey with me. I love you guys! #weightlossjourney #weightlosstransformation #ketotransformation #fitmom

A post shared by Jenna Jameson (@jennacantlose) on

Thought I’d post a #motivationmonday #beforeandafter of my total weightloss. On the right I weight 187. On the left I’m a strong 130. I was lethargic and struggled with the easiest of tasks like walking in the beach sand with Batelli. 😞 I felt slow mentally and physically. I took the pic on the right for a body positive post I was going to do and decided against it because I felt anything but fucking positive. I’m now a little under 4 months on the #ketodiet and it’s not only given me physical results, I feel happier, smarter, and much more confident. I also want to let y’all know how much your amazing support means to me. I know you loved me heavy, and now… but your journeys inspire me to keep inspiring you. Thank you for going on this journey with me. I love you guys! #weightlossjourney #weightlosstransformation #ketotransformation #fitmom

A post shared by Jenna Jameson (@jennacantlose) on

“I also want to let y’all know how much your amazing support means to me,” she wrote on Instagram last week. “I know you loved me heavy, and now … but your journeys inspire me to keep inspiring you.”

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Plastics blamed for rise in penis malformations

Plastics blamed for the rise in penis malformations: Small study claims boys are more likely to be born with the disorder if they were exposed to chemicals in the womb

  • Hypospadias is a urethra abnormality, when the opening of the penis forms on the underside rather than on the tip
  • A new Israeli study offers a theory for the cause of rising rates
  • Other experts say the association has merit but the study ‘takes a huge leap of faith’ to reach its conclusion 

A small study has shown a link between increasingly common penis malformations and chemicals in plastics, furniture and TVs. 

Hypospadias is a urethra abnormality, when the opening of the penis forms on the underside rather than on the tip. 

The condition affects around one in 200 male children – but rates are soaring, and in some regions, including Australia and the UK, they have doubled since 1980. 

Now, in a new study published today in the Journal of the American Medical Association, an Israeli research team claims to have concrete evidence of a link between hypospadias and PDBEs, the chemicals found in plastics and fragrances.

The controversial study has caused a flurry of excitement and concern in the medical community, with many acknowledging that the link has merit, but warning that there still is not enough evidence to unequivocally connect the two.  

Hypospadias is a urethra abnormality, when the opening of the penis forms on the underside rather than on the tip. A new study offers a theory for the cause of rising rates (file image)

Hypospadias is present at birth. 

In milder cases, the urethra forms not far from the tip of the penis, but in others it can be much further down the shaft, or even on the scrotum. 

Surgery can be performed when the child reaches six months old, though urologists are constantly pushing for improvements since patients routinely report feeling embarrassed later in life about their penis’s post-operation appearance.

The biggest push, though, is for research to uncover the factors causing the condition.  

This new study by the Maccabi Research Institute in Tel Aviv claims to have found strong evidence to support a popular theory: that modern life is to blame for this defect. 

PDBEs (polybrominated diphenyl ethers) have been a popular target in all kinds of medical research papers in the past couple of decades, particularly ones relating to fetal development. 

They are a set of chemicals with powerful properties that disrupt hormones, and yet since the 1970s they have been added to all kinds of products to make them less susceptible to flames.  

As time passes, these chemicals rub off the products and accumulate on the surface. In the case of a TV, for example, that becomes risky because TVs gather dust, and that dust can mix with the PDBEs, which humans may inhale. 

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At one point, most couches, plastic bottles, rugs and TV were made with PDBEs in some shape or form.

As the dangers of PDBEs have emerged, more restrictions have been placed on how they can be used to limit our exposure. However, avoiding them completely remains complicated. Indeed, a study last week showed evidence of PDBEs in farmed fish, despite US and EU restrictions on PDBEs in fish-farming waters. 

To put it mildly, there is still plenty of panic about the subtle ways we experience these chemicals, and it’s 

To assess whether there could be a link between the two, lead authors Shirley Poon, PhD, and Gideon Koren, MD, analyzed 152 mothers of boys with hypospadias, and 64 controls. 

They analyzed the levels of PDBEs in their hair – a known noninvasive biomarker for long-term PDBE exposure. 

They also looked at each child’s medical records, and interviewed each mother with a questionnaire.

Based on the data they collated, they concluded that ‘mothers of children with hypospadias were exposed during pregnancy to significantly higher levels of PBDEs’. 

The results triggered a swell of reactions from other scientists in the field of pediatrics and pathology. 

Many acknowledged that this is hardly an unfounded theory. In fact, it comes just days after an Australian study claimed to prove a connection between plastics and hypospadias in animals. 

But most cautioned that more needs to be done to firm up this connection if it is indeed valid. 

‘It is an important question as these chemicals are very prevalent in the home environment. If they are doing harm it is important that further research be done into the question,’ said Professor Jean Golding, Emeritus Professor of Pediatric and Perinatal Epidemiology at the University of Bristol. 

But, Prof Golding cautioned, there are many limitations to the study, taking issue with the imbalance between cases of hypospadias and control, and the fact that they did not take controls and cases from the same population. 

Professor Ieuan Highes, Emeritus Professor of Pediatrics at the University of Cambridge, said: ‘On first sight, the results are persuasive of adverse effects from PBDEs in the environment on development of the male genitalia before birth. But, hypospadias can be associated with a myriad of other factors not least low birth weight where the association is strong.’

He added: ‘The authors part compensated for this by more detailed analysis and while there was still an association with PBDEs exposure, the link was weaker. 

‘There are also known genetic causes of hypospadias as well as the condition running in families which was not addressed in this study. 

‘In discussing why PBDEs may affect male development, the authors refer to how these compounds can interfere with the estrogen ( female hormone) pathway, yet it is androgens ( the male hormone) which are essential for male development during a male programming window in early pregnancy.’ 

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Experimental drug could reverse hair loss caused by fatty diets 

Could this drug undo the damage of a fatty diet? New molecule reversed hair loss, cleared up skin, and banished grays in junk food-addicted mice

  • Mice that were fed a Western diet, as opposed to rat chow, developed gray hair,  as well as hair loss and skin inflammation almost immediately 
  • They were then given a compound that stops the production of a fat-and-sugar-molecule known as GSL
  • GSLs affect the body’s ability to rid itself of cholesterol that clogs blood vessels, and help to regulate hair, skin and eye color
  • When given this molecule, the mice regrew their hair, the color changed from gray to white, and their skin lesions healed 

A new drug could undo the damage of a fatty diet by reversing signs of aging, a new study has found.

Scientists say mice almost immediately lost their hair and experienced skin inflammation after eating a Western diet, but an experimental compound was successfully able to treat them.

The drug halts the production of a type of molecule that doesn’t allow the body to rid itself of cholesterol and is responsible for regulating hair, skin and eye color.

The team, from John Hopkins University School of Medicine in Maryland, says its findings could lead to either oral or topical medications that reverse aging rather than just slowing down the process. 

A new drug could undo the damage of a fatty diet by reversing signs of aging including hair loss, graying hair, and skin inflammation, a new study has found (file image)

For the study, the team genetically modified the mice so they would develop atherosclerosis, a disease what occurs when the arteries narrow due to plaque buildup on the inner walls.

While the exact cause is unknown, certain factors are known to trigger atherosclerosis including high amounts of fats, cholesterol and sugar in the blood, according to the National Heart, Lung and Blood Institute.

Next, the mice were split into two groups with one group being fed rat chow and the other group given a Western diet high in fat and cholesterol.

The mice that were fed the Western diet and almost immediately experienced skin lesions, graying hair and a large amount of hair loss – and at an accelerated rate.

‘Our findings show that a Western diet causes hair loss, hair whitening and skin inflammation in mice,’ said Dr Subroto Chatterjee, a professor of pediatrics at the Johns Hopkins University School of Medicine.

‘We believe a similar process occurs in men who lose hair and experience hair whitening when they eat a diet high in fat and cholesterol.’

The effects became more severe the longer the mice stayed on the Western diet. After 36 weeks, 75 percent of the mice on the high fat diet experienced skin lesions and hair loss.

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To treat the mice, they were given a compound called D-PDMP, a man-made drug that stops the production of glycosphingolipids, or GSLs.

GSLs are fat-and-sugar molecules that are found in the skin and in other cell membranes.

They affect the body’s ability to use, transport and rid itself of cholesterol that clogs blood vessels. 

Researchers gave the mice the compound either in capsule or in liquid form, and said the capsule was the more effective treatment – helping the mice regrow their hair, turn the color back from gray to black, and reducing their skin inflammation.

The team says that because this research has only been conducted on animals, more studies need to be done to see if the same holds true for humans.

But they believe their findings do offer the possibility of medications – topical or oral – being created with D-PDMP to treat damage caused by hair loss or skin inflammation.

‘Further research is needed, but our findings show promise for someday using the drug we developed for skin diseases such as psoriasis, and wounds resulting from diabetes or plastic surgery,’ said Dr Chatterjee.   

‘Hopefully someday in the future this can mean faster, more effective recovery from baldness, hair whitening in aging populations and wound healing.’ 

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Former Porn Star Says Her Breast Implant Was Deflated By Rogue Hockey Puck at Stanley Cup Game

Former porn star Mia Khalifa has a unique and painful souvenir from this year’s NHL playoffs.

In a new interview with the U.K.’s Daily Star, Khalifa — now the cohost of podcast Sportsball — revealed that she’ll undergo reconstructive surgery after allegedly being hit by a flying hockey puck earlier this year.

“I was sitting behind the glass during a game, and it came shooting over the glass and it caught me so off guard and I had no idea it was coming,” said Khalifa, 25. She added to the Star, “I grabbed my chest and I didn’t want to let go, because I felt like if I did let go blood was going to be everywhere.”

Khalifa noted to the outlet that pucks are “really heavy,” and speculated that it was traveling at about 80 mph. when it allegedly struck her.

“My left breast is slightly deflated now and I will be getting it fixed next year,” she said.

A rep for Khalifa told PEOPLE, “It is a self-diagnosed injury that occurred as she described in her Instagram post from May.”

Alongside the May photo of Khalifa taken at Capital One Arena, she wrote at the time, “Also, I got hit in the boob with a puck during the game, and I’m 80% sure it ruptured an implant. But the good news is, I got a game used puck from a Capitals Stanley cup playoff game. Worth it.”

She echoed to the Star, “I got to take it home, it was the single greatest souvenir any hockey fan can get: a game-used puck that comes at you and hits you.”

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Lab identifies new model to study connectivity in the developing brain

In a paper published Tuesday in the journal eLife, Michael Francis, PhD, and colleagues highlight a new role for the protein NRX-1, a synaptic organizer in the nervous system of the nematode C. elegans.

Dr. Francis, associate professor of neurobiology, details how NRX-1, the nematode equivalent to the neurexin protein in mammals, must be present for the formation of synaptic connections between specific types of neurons.

In addition, the researchers found that when NRX-1 is present, the protein encourages dendritic spine-like growths, similar to those in the human brain, to make these neuron-to-neuron connections. When the protein is absent, these partner-specific synaptic connections are not made.

Francis hopes that the discovery will enable researchers to use the nematode to study the genes that control nervous system connectivity and spine outgrowth. Nematodes have a simpler nervous system than humans. Using the nematode could advance research capabilities that focus on whether neurodevelopmental and neuropsychiatric disorders, such as autism spectrum disorder, arise from defects in the establishment of connectivity in the developing brain.

“We can use the experimental strengths of this simple system to identify novel mechanisms that are important for setting up connectivity. Knowing more about the connections enables us to now ask deeper questions about the processes underlying brain development,” Francis said.

Previously, scientists, using a mouse model, discovered that neurexin proteins promote synaptic connectivity, but their roles in this process have been incompletely understood. By attaching a green fluorescent protein to the receptors at C. elegans synapses, Francis was able to study individual synapses in the living worm and determine whether there are specific genes required to establish partner-specific connections.

Francis and colleagues also saw that when NRX-1 is present, there is growth of dendritic spine-like structures that had not been previously demonstrated. This leads Francis to believe that neurexin might be involved in the growth in dendritic spines in the mammalian nervous system and that growing spines may be preferentially targeted to neurons that have neurexin.

“This opens up the opportunity to use the less complicated nematode system to understand how dendritic spines grow in a well-defined, genetically tractable system,” he said.

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Study shows role of enzyme in prostate cancer growth

A new USC School of Pharmacy study led by University Professor Jean Chen Shih offers new evidence that the monoamine oxidase-A enzyme (MAO-A) pathway could be an important target in treating prostate cancer.

Pioneering work previously conducted by Shih revealed the role the MAO-A gene plays in depression and other mental illnesses, as well as autism and aggression.

Research has shown increased MAO-A expression in prostate cancer, glioma and classical Hodgkin lymphoma. Yet the biological function of MAO-A in cancer development remained unknown—until now.

In a study published in Oncogene, Shih and her co-investigators examined the role MAO-A plays in the progression of prostate cancer. The findings show that inhibition of MAO-A expression reduces prostate cancer development by decreasing cell proliferation and cancer stem cells.

Because MAO-A inhibitors are successfully being used to treat other diseases linked to this enzyme, such as depression, Shih and her collaborators believe the right inhibitors also hold the potential and in treating prostate cancer and reducing prostate cancer growth.

“We’ve found MAO is increased in prostate cancer, glioma and lymphoma. In these cancers, we think the patient may benefit by treatment with MAO inhibitors,” explained Shih, who holds the Boyd P. and Elsie D. Welin Professorship in Pharmaceutical Sciences and serves as director of the Center for USC-Taiwan Translational Research. “We are eager to pursue preclinical and clinical studies.”

Treating prostate cancer with antidepressants

According to the American Cancer Society, more than 29,000 deaths from prostate cancer will occur in 2018, putting the disease just behind lung cancer as the leading cause of cancer death in American men. One in nine men will be diagnosed with prostate cancer during his lifetime.

“The results of this study are significant as they suggest that the MAO-A pathway is an important target in prostate cancer,” said study co-author Mitchell Gross of the Keck School of Medicine of USC. “This is especially exciting because MAO inhibitors are already FDA-approved and available to treat depression.”

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Researchers report unraveling the immune recognition of nucleic acid nanoparticles: Particle-specific immune responses may be ‘an alphabet for talking to the immune system’

An extensive experiment testing the immune effects of a broad group of lab-designed nucleic acid nanoparticles did not find a strong, uniform immune response, as had been predicted. Instead, the tests found varying and specific responses from different immune cells, depending on each particle’s shape and formulation, a finding that may encourage further study of the particles’ therapeutic use.

In addition, the researchers believe that they may have discovered an “auxiliary” system for managing immune response — a molecular “alphabet” for communicating with the human immune system.

The findings were recently reported by Enping Hong, Ankit Shah, and Marina Dobrovolskaia of the Frederick Laboratory for Cancer Research, Emil Khisamutdinov of Ball State University and Justin Halman and Kirill Afonin of the University of North Carolina at Charlotte in the journal Nano Letters.

The idea has been around for a while that selected segments of RNA or DNA could be used therapeutically — “therapeutic nucleic acids” — to affect gene or cell function. Unfortunately, in clinical trials most of these proposed therapeutic molecules have proved to have an extreme side effect — they provoked a strong, often fatal reaction from the human body’s immune cells.

More recently, nanotechnologists have proposed designing self-assembling nanoparticles with the potentially therapeutic RNA or DNA sequences, combining the effects of several sequences into a targeted drug, giving multiple effects in a single particle, shaped into various designer forms — squares, triangles, cubes, and other structures. These potentially powerful therapeutic particles have been slow to be tested however, because researchers have theorized that they were likely to have the same “immunotoxic” effects as the natural nucleic acid fragments.

However, some nanoscientists questioned whether the projected immune reactions would necessarily be the case because of the complexities of immune system recognition and unique properties created by assembling traditional materials into nanoparticles of various shapes and structures.

“Even if nucleic acid nanoparticles are composed of components with known immunological toxicities, once you combine them and reformulate them, the nanoformulation becomes a completely different beast,” said Afonin, one of the paper’s corresponding authors.

“Our findings showed that, while some of the predictions were correct, many were completely wrong,” noted Afonin. “You can’t predict the immunotoxicity of nucleic acid nanoparticles purely by analyzing the responses to naturally produced DNAs and RNAs. We came up with some unexpected results.”

To test the immunotoxicity of the particles and perhaps find clues for the mechanisms involved in immune cell response, Afonin and his colleagues selected a “library” of 25 different DNA or RNA nucleic acid nanoparticles designed by researchers in the field, carefully picked to “address all possible links” between their molecular properties and immune reactions. The library included a representative sampling of planar (flat), globular and fibrous (string-like) particles, with different sizes and molecular weights, as well as differing in a variety of critical chemical attributes. The particles were introduced to immune cells (peripheral blood mononuclear cells) from the blood of 60 unique human donors and monitored for the production of 29 different cytokines.

The details of the findings were revealing regarding the immunotoxicity of the particles because the immune response varied. But the results also revealed information regarding specific behavior of various immune cells.

A fundamental finding was that “naked” nucleic acid nanoparticles (unattached to other biological molecules) caused no immune response at all — because, the team found, unlike naturally occurring fragments of DNA or RNA, the constructed particles could not enter any immune cell without some kind of “carrier” molecules that allowed their entry. Effectively, plain nucleic acid nanoparticles are “invisible” to the human immune system.

Once the particles were paired with a carrier molecules, however, they were able to enter the cells, and elicited clear responses, as the researchers hoped. “The question is when we send this particle inside the human cell, what does the cell, particularly the immune cell, do?” Afonin wondered. “Does it see a particular shape as a threat?”

The results show that particle size, shape, 3-D structure (cubes, for example, compared with planar squares), DNA or RNA composition, and the chemical nature of how the particles were assembled (“connectivity”) all had distinctive effects on immune response and on which immune cells responded.

Among the details uncovered was the finding that particles composed of DNA tended to cause less immune response than those of RNA. RNA rings (flat structures) and RNA fibers caused less immune response than RNA cubes (globular structures). In further detail, DNA cubes induced the cytokine production of type I interferons alpha and omega, but only RNA cubes could induce type I interferon-beta or type III interferon-lambda. The different cytokines produced indicated that the differences in particles had a selective effect on that type of immune cell affected.

While the findings are scientifically important, the researchers stress that the new information has implications for future practical applications.

“Our findings highlight the key parameters that inform the way nucleic acid nanoparticles interact with the immune system,” the paper states. “These new insights improve the current understanding nucleic acid nanoparticles immunostimulatory properties, and pave the way to development of a new auxiliary molecular language that can be expressed through the script of rationally designed nucleic acid nanoparticles.”

“We have an alphabet to directly communicate with the immune system,” said Afonin. “Now we have to figure out the syntax of this new language; how to assemble these letters into the words, put sentences together, combine them into the paragraphs, and eventually, how to write a story. But right now we have an alphabet — it’s just the beginning, but I think this is fundamental work.”

Afonin points out that an “alphabet” that describes immune response to specific particle designs may naturally be useful for avoiding adverse reactions, but has more potential for situations where a response is actually desired (in the case of vaccines, for example) and has still more possibilities when treatment requires specific messaging to trigger a very specific immune response.

“If you need to deliver a drug, you may want the carrier to be non-immunogenic. We can tell you exactly which particle you can use for that,” he said. “But if you want to stimulate the immune response, for example to activate the immune system against cancer… then you can use certain particles which will activate the immune response but avoid inflammation. We can produce interferons, but not inflammatory cytokines, for example.

“This is like sharpshooting,” he explained. “You will be shooting for a particular cytokine, without touching others. This is like a letter or a word, like a text message that we send to the immune system. The immune system will read your message and text back with the interferon.”

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Fat production and burning are synchronized in livers of mice with obesity

Mice fed a fattening diet develop new liver circadian rhythms that impact the way fat is accumulated and simultaneously burned, according to a new study published in Cell by researchers in the Perelman School of Medicine at the University of Pennsylvania. The team found that as liver fat production increases, surprisingly, so does the body’s ability to burn fat. These opposing physiological processes reach their peak activity each day around 5 p.m., illustrating an unexpected connection between overeating, circadian rhythms, and fat accumulation in the liver.

“We know that obesity leads to accumulation of fat in the liver, which can cause inflammation and possibly hepatitis, liver failure, and even liver cancer,” said senior author Mitchell Lazar, MD, PhD, director of Penn’s Institute for Diabetes, Obesity, and Metabolism, and chief of the division of Endocrinology, Diabetes and Metabolism. “This is rapidly becoming a huge problem, as these conditions can lead to an increased need for liver transplantation, and worse, can be deadly.”

While one billion people worldwide are adversely affected by malnutrition, there are another billion who experience excess calorie intake, or “overnutrition,” which leads to obesity and other metabolic disorders including type-2 diabetes, cardiovascular disease, fatty liver, hypertension, and cancer. “Studying the harmful effects of overnutrition is a top priority, especially in the United States where metabolic disorders have reached epidemic proportions,” Lazar said.

The circadian rhythms that fat creation and burning follow are physiological processes that occur with about every 24 hours. At the molecular level, these cycles involve feedback loops of core clock proteins expressed in virtually every cell of the body. This internal timekeeper functions to integrate environmental stimuli and genetic information to control rhythmic gene expression in a tissue-specific way.

A misalignment of this schedule is increasingly recognized as a risk factor for metabolic disorders. For example, night shift workers and individuals with sleep disorders have an increased risk of metabolic diseases. Understanding the mechanisms that impact the relationship between circadian rhythms and metabolic disorders are necessary for the development of meaningful therapeutic strategies for treating obesity-related diseases.

“We speculate that the diet-induced synchronization of these opposing liver fat metabolic processes is a response to an environment of overnutrition, leading to fat burning outpacing fat accumulation in the liver,” said first author Dongyin Guan, PhD, a postdoctoral fellow in Lazar’s lab.

The 24-hour clock aspect of this physiology informs the practice of chronotherapy, which involves administering drugs at times when they are most impactful and tolerated in order to enhance effectiveness and reduce toxicity. The team discovered that the rhythm of fat burning is controlled by a protein called PPAR-alpha, which is the target of drugs called fibrates, which are already used to lower lipids in the blood. The amount of PPAR-alpha in the liver also peaked around 5 p.m.

From this coordination, Lazar’s team asked whether there would be a benefit to giving short-acting PPAR-alpha drugs at the specific time of day when PPAR-alpha is at its highest level. The researchers observed that a short-acting PPAR-alpha drug reduced liver fat more when it was given in the afternoon than when it was given in the morning.

Similar to how statins (cholesterol-lowering drugs) are prescribed to be taken at bedtime, “our results support that due to the rhythmicity of PPAR-alpha, drugs that lower liver and blood lipid levels could be more effective at specific times of day,” Lazar said. “Following this principle more closely to treat liver metabolic disease may indeed benefit patients, as recent studies have shown that PPAR-alpha expression oscillates in the human liver.”

The study was supported by the National Institutes of Health (R01-DK045586, R01-HL54926, R01-DK098542, F32DK116519), the JPB Foundation and an American Diabetes Association Training Grant (1-17-PDF-076, 1-18-PDF-132).

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Nail Cancer Is Real, Miss Illinois Karolina Jasko Had This Type Of Melanoma

The beauty queen was just a teenager when she got the shocking diagnosis.

The reigning Miss Illinois USA 2018, Karolina Jasko, is going public with her battle with melanoma — which she surprisingly got on one of her fingernails.

Yes, nail melanoma is a real disease.

Jasko developed a black vertical line on her right thumbnail when she was just a high school senior. However, she didn’t seek medical attention until it became infected. That’s when she was officially diagnosed.

Fortunately, after three surgeries, doctors were able to get rid of the skin cancer, but she lost her thumbnail because of it.

“I’m a little self-conscious about it, but I was lucky,” said the 20-year-old in a news release from the American Academy of Dermatology.

“The doctors originally thought they would have to remove my whole thumb, and you never realize how much you use your right thumb until you think about losing it. And if I had waited any longer to see a doctor and have my first surgery, the melanoma could have spread through my whole body, and it would have been a lot worse.”

As with all cancers, early detection is key to beating nail melanoma, which is often overlooked and diagnosed too late.

“It’s important to regularly examine your whole body for signs of melanoma and other skin cancers, and that includes your nails,” explained board-certified dermatologist and nail specialist Shari Lipner, M.D., Ph.D., who practices at New York City’s Weill Cornell Medicine.

“Because early detection plays such a big role in nail melanoma prognosis, it’s important to keep an eye on your nails and be aware of any changes to them.”


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The American Academy of Dermatology said that the main sign of nail melanoma, which can occur on both fingernails and toenails, is a new brown or black band in the nail. Other symptoms can include the “presence of pigment on the adjacent skin, splitting or bleeding of the nail, or infection-like symptoms such as drainage, pus, and pain.”

While dark bands can just be from something benign like blood under the nails, a bacterial or fungal infection, or residual pigment, if the band grows wider or darker, Lipner suggests seeing a dermatologist right away.

Anyone can develop nail melanoma, but it seems to occur more frequently in older adults and people with skin of color.

Lipner said that the disease’s two main risk factors are nail trauma and a personal or family history of melanoma.

In Jasko’s case, her mother previously suffered melanoma.

“People may not realize that you can get melanoma in your nails, but it’s important to be aware of that risk,” she said.

“If you have the slightest concern about something on your nail, go and get it checked out by a dermatologist [as] it could end up saving your finger — or your life.”

Jasko, who is studying psychology at the University of Illinois at Chicago, competed in the Miss USA pageant this past May.

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