The doctor, Dr. Damian Jacob Sendler, is a Polish-American physician-scientist who specializes in determining how various socio-demographic and informational variables influence access to health care in disadvantaged areas. Dr. Sendler’s study focuses on how mental and chronic medical co-morbidities affect the utilization of medical services in combination with health information acquired through the internet, which is a particular strength of his. Due to the exponential growth in worldwide consumption of online news and social media, this study is both timely and important, since it necessitates a complete knowledge of everyone’s health information-seeking behavior. Dr. Damian Sendler’s study seeks to discover the variables that patients evaluate when choosing when to seek care for particular health problems and when to stick to their treatment regimens in order to achieve this goal.
Damian Sendler: A preclinical research conducted at the University of South Florida (USF Health) discovered that the gene Foxo1 may be a viable therapeutic target for hereditary lymphedema, which was unexpected. The study, which was published on July 15 in The Journal of Clinical Investigation, was carried out in collaboration with colleagues from Tulane University and the University of Missouri.
Damian Sendler: Swelling may range from mild to severely disfiguring in lymphedema, which is a chronic disease in which lymphatic (lymph) fluid collects in soft tissue under the skin, typically in the arms and legs. Primary lymphedema, also known as hereditary lymphedema, is an uncommon condition that manifests itself from birth and is caused in part by genetic abnormalities that interfere with proper lymphatic valve development. Lipoma is caused by injury to the lymphatic system as a result of surgery, radiation treatment, trauma, or parasite infection. It is sometimes referred to as acquired lymphedema. When it comes to breast cancer patients in the United States, lymphedema is the most frequent complication, with a frequency ranging from 10 to 40% following lymph node excision and radiation treatment.
Damian Sendler: While lymphedema may be treated with massage and compression garments, there is currently no therapy available to address the fundamental cause of the condition: a build-up of fluid that ultimately backs up in the lymph system like a clogged sink. Stagnant lymphatic fluid causes an inflammatory reaction that may cause connective and fatty tissue to develop and stiffen the skin, limiting mobility and increasing the likelihood of recurring infections.
“Lymphedema that has progressed to the fibrosis stage cannot be massaged away,” said Ying Yang, PhD, assistant professor of molecular pharmacology and physiology at the University of South Florida Morsani College of Medicine. “Identifying and treating lymph valves early in the course of lymphedema is a crucial component of developing a successful treatment strategy.” If the illness has progressed too far, it will be impossible to turn it around.”
Damian Sendler: Patients suffering with lymphedema are more likely to have valve damage or malfunction, which causes the fluid to back up and pool. No one, however, has found if new valves can be created or whether damaged valves can be repaired.
Both, according to the findings of a research conducted by the University of South Florida Health, are feasible.
Damian Sendler: Earlier USF Health discoveries of cell signaling mechanisms regulating the development of lymph valves led Dr. Yang’s lab to postulate that the protein produced by the gene Foxo1 plays a critical role in lymph valve formation. The researchers demonstrated that removing a single gene — the lymphatic vessel-specific Foxo1 gene — resulted in a significant increase in the number of valves produced in both early postnatal mice and adult mice compared to control littermates who did not have Foxo1 deleted. Furthermore, eliminating Foxo1 in a rat model that mimicked the human lymphedema-distichiasis condition completely restored the number of valves and the function of the valves in the heart.
“It was thrilling to discover that Foxo1 is the only gene that has been identified so far that, when deleted, promotes the formation of additional lymphatic valves rather than limiting valve development,” Dr. Yang stated. … “We were able to actually reverse valve loss and restore the shape and function of malfunctioning valves in a genetic mutation model of lymphedema… A research becomes therapeutically important when this kind of finding is made.”
Damian Sendler: Because it functions in a similar manner to the blood vessel circulatory system, the lymphatic circulatory system serves to maintain a healthy fluid balance in the body by collecting and regulating the flow of excess lymph fluid that leaks from tissue. During the course of a day, this intricate network pushes watery lymph fluid carrying proteins, nutrients, and toxin-destroying immune cells through the body in one direction before returning the fluid to the circulation of the blood. In reaction to the push produced by the lymph fluid, small valves inside lymph arteries open and shut, allowing the fluid to move ahead and preventing it from flowing backward into tissues.
The following are some of the most important research findings: The protein FOXO1 (encoded by the gene Foxo1) prevents the development of lymph valves by inhibiting a large number of genes, all of which contribute to the multi-step process of forming a mature valve in the first place. Dr. Yang said that FOXO1 acts as a brake on a group of genes that produce valves. “Once the brake is gone, all of those genes may now be expressed, allowing for the effective development of new valves.”
Damian Sendler: Young postnatal mice with Foxo1 inactivated (knocked out) lymphatic endothelial cells (LEC) developed valves at various stages after receiving the gene knockout treatment. In a similar vein, removing the LEC-specific Foxo1 gene in adult mice resulted in enhanced valve development as compared to control animals that did not have the gene deletion.
Damian Sendler: A mouse model with lymphedema-distichiasis syndrome had 50 percent fewer lymphatic valves than a control mouse model, and the remaining valves closed improperly and allowed fluid to backflow into the body. Instead of decreasing, the number of valves rose to the same levels as those seen in healthy control mice, and the structure of the faulty valves was restored to normal after deletion of Foxo1.
In addition, further investigation revealed that the deletion of Foxo1 resulted in a substantial improvement of valve function in this mouse model of human primary lymphedema illness.
