Polyploidy can be a double-edged sword in cancer

Polyploidy is a state where a cell contains more copies of the genetic material than the usual "diploid" cell, which contains two copies. Polyploidy often occurs in human diseases and cancers, and its effect on cell fate was unclear. Now, however, researchers from Japan have shown that polyploidy can be a double-edged sword when it comes to cancer and its treatment.

In a study published this month in Cell Death Discovery, researchers from Osaka University have revealed that polyploidy is closely linked to the accumulation of damage to the genetic material within the cell, while also allowing those cells to tolerate higher levels of this DNA damage.

Polyploidization can occur naturally in organs such as the liver, where it can be an advantage, allowing liver cells to tolerate high levels of exposure to the toxic molecules processed by the liver as part of its function. However, this polyploidy can also be an origin of carcinogenesis, and these cancers are frequently resistant to anti-cancer drugs.

Using a human liver cell line, the team showed that the occurrence of polyploidy did not always lead to the process called "senescence", by which cells stop dividing. The presence of DNA damage caused difficulties when cells divided, thus increasing the likelihood of mistakes arising and polyploidization developing. At the same time, the presence of polyploidization increased the amount of DNA damage that occurred, because of the stress the extra genomic material placed on the process of cell division.

However, the team also discovered that polyploid cells can tolerate a greater amount of DNA damage than diploid cells. As diploid cells accumulate damage, they eventually stop cell division and begin to show a phenotype known as the senescence-associated secretory phenotype, or SASP. It took a greater level of DNA damage for polyploid cells to show growth arrest or SASP.

As polyploid cells contain more copies of the genetic information than diploid cells, any DNA damage that accumulates is less likely to occur in all of the copies of any essential gene, allowing the cells to survive for longer."

Kazuki Hayashi, lead author of the study

 Reference: News Medical

Scientists make 1-of-a-kind immune cells to guard transplants from attack

In a first, scientists have designed immune cells that protect stem cell transplants from being rejected by the body — and they could someday open the door for a cure for diabetes.

The new cells, which were able to protect insulin-producing cells transplanted into mice, are an early "proof-of-concept," said study co-author Audrey Parent, an associate professor at the University of California, San Francisco (UCSF) Diabetes Center.

  But if shown to be safe and effective in people, the designer cells could one day be used to protect transplanted tissues from attack, reducing or eliminating the need for drugs that suppress the immune system. That, in turn, could pave the way to a cure for diseases like type 1 diabetes. 

In type 1 diabetes, immune cells, known as killer T cells, destroy pancreatic beta cells, which make insulin. In recent years, scientists have progressively inched closer to replacing destroyed beta cells with new cells derived from stem cells, which can be made to turn into any type of cell in the body.

In June, for instance, scientists reversed type 1 diabetes in a person by reprogramming their fat cells, while the Boston-based company Vertex Pharmaceuticals recently launched a pivotal, large-scale trial testing whether reprogrammed stem cells can eliminate the need for insulin in those with type 1 diabetes.

But before such stem-cell transplants can be widely used, scientists need to solve one big problem: In type 1 diabetes, killer T cells have been trained to target beta cells and have already destroyed those cells once. The transplanted cells need protection from this immune attack, so for now, patients need strong drugs that suppress the immune system. However, these drugs leave patients open to dangerous infections and are toxic to the kidneys and other organs.

To get around this problem, Parent and colleagues engineered T cells in the lab that protected the transplanted cells — known as a graft — from attack.

"We took an immune cell and changed the machinery inside it to make it a protective cell instead of a killer cell," Parent told Live Science. "And then we targeted it to the graft." Essentially, the designer cells act as bodyguards.

The bodyguards zero in on beta cells because they recognize a specific protein, called CD19, that the researchers added to the beta cells. When the bodyguard cells grab onto CD19, they then crank out a molecule that inhibits killer T cells.

The guards also make a protein that sops up an inflammatory chemical that normally helps activate killer T cells. This anti-inflammatory protein also tells the guards to replicate, creating a positive feedback loop that reinforces their ranks, Parent said.

To test their guards in a living organism, the researchers then took beta cells derived from stem cells and implanted them into mice. They then sent killer T cells to attack the transplanted beta cells. In one group of mice, they also injected their designer cells to defend the transplants.

In the mice not given designer cells, the killer cells quickly wiped out all the beta cells. But in the mice injected with designer cells, the transplants lived at least 35 days, and the mice were still producing insulin at that time, researchers reported in the study, published Thursday (Dec. 5) in the journal Science.

The results show it is possible to engineer T cells that can protect transplanted tissue, Parent said.

However, one challenge is finding a unique protein target to activate the designer cells, Parent said, as most potential targets are found on cells in multiple places in the body. That raises the chances that their designer cells will activate elsewhere in the body, beyond the transplants. That could pose a problem if, for instance, cells with the protein target become infected or cancerous, but can't be cleared because they are being protected by the guard cells. Transplant cells could be engineered to have a "kill" switch for those cases, but other cells in the body wouldn't have this switch.

Follow-up work may address this problem. For instance, the team could engineer an artificial target that would be found only on the transplanted beta cells and nowhere else, study co-author Wendell Lim, a biochemist and director of the UCSF Cell Design Institute, told Live Science in an email.

In a separate study, also published Thursday in Science, Lim and colleagues showed that similar designer T cells could target brain tumor cells while leaving healthy brain cells alone. The cells could also deliver anti-inflammatory chemicals to brain cells in mice with a disease similar to multiple sclerosis.

Looking forward, the team is also interested in seeing how this approach works against other autoimmune diseases fueled by inflammation, such as rheumatoid arthritis, as well as Crohn's disease and other inflammatory bowel diseases, Lim added. But it will be several years before these ideas can be tested in humans, he said.

"This work opens up a new avenue for treating inflammatory diseases in a targeted way," he said," but lots of pieces need to be put together and tested to come up with effective therapies."

Reference: Live Science: Story by Tia Ghose 

Sea buckthorn is a small, orange berry that is packed with nutrients and has been used for centuries in traditional medicine. It is rich in vitamins, minerals, antioxidants, and fatty acids, making it a superfood for overall health.

The Nutritional Benefits of Sea Buckthorn

Sea buckthorn is a small, orange berry that is packed with nutrients and has been used for centuries in traditional medicine. It is rich in vitamins, minerals, antioxidants, and fatty acids, making it a superfood for overall health.

Vitamins and Minerals

Sea buckthorn is particularly high in vitamin C, vitamin E, vitamin A, and several B vitamins. These vitamins are essential for immune function, skin health, and overall well-being. In addition, sea buckthorn contains minerals like potassium, calcium, and magnesium, which are important for various bo

The Power Of Sea Buckthorn: Nutritional Benefits And Uses 

Discover the nutritional benefits of sea buckthorn and how it can improve your overall health. Learn about its vitamins, minerals, antioxidants, and fatty acids. 

The Nutritional Benefits of Sea Buckthorn

dily functions.

Antioxidants

Sea buckthorn is loaded with powerful antioxidants, such as flavonoids and carotenoids, which help protect cells from damage caused by free radicals. These antioxidants can reduce inflammation, lower the risk of chronic diseases, and promote healthy aging.

Fatty Acids

Sea buckthorn is one of the few plant sources of omega-7 fatty acids, which are beneficial for heart health and can help improve cholesterol levels. It also contains omega-3 and omega-6 fatty acids, which are essential for brain function and reducing inflammation in the body.

Uses in Diets and Recipes

Sea buckthorn can be consumed in various forms, including juices, oils, and supplements. It has a tangy, citrus-like flavor that can add a unique twist to smoothies, salads, and desserts. Sea buckthorn oil is often used topically for skin care due to its hydrating and anti-aging properties.

Medical Disclaimer: All content on this Web site, including medical opinion and any other health-related information, is for informational purposes only and should not be considered to be a specific diagnosis or treatment plan for any individual situation. Use of this site and the information contained herein does not create a doctor-patient relationship. Always seek the direct advice of your own doctor in connection with any questions or issues you may have regarding your own health or the health of others.  

Reference: This Nutrition: 

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