Modulating the senescent and secretory phenotypes of fibroblasts using ultrasound

Abstract

Cancer treatment and wound management are two of the biggest problems in healthcare today. Cancer has been referred to as "wounds that do not heal" because it uses the stroma-gathering process to obtain the stroma necessary for growth and survival. Current research has connected replicative senescence in the elderly to chronic wounds and cancer. With aging, a process known as replicative cellular senescence causes the cells to reach a point where they are unable to divide and stop proliferating. Senescence-Associated Secretory Phenotype (SASP), which is manifested in senescent cells, demonstrates a clear change in the profile of secreted proteins, and arises from a restorative programme during aging to a dysregulated cascade that encourages tumorigenesis and chronic inflammation. Low intensity pulsed ultrasound (LIPUS), which is safe and economical in comparison to conventional therapies, has been utilised in several trials to enhance wound healing. In a chronic wound, LIPUS can boost the production of growth factors and proteins while reducing the expression of inflammatory cytokines. In this study, we investigate whether ultrasound alters fibroblast senescence and SASP in a manner that might be advantageous for the treatment of chronic wounds and other age-related diseases. Using the anti-cancer medication cisplatin to induce senescence in human foreskin fibroblast (HFF), which was then exposed to LIPUS for three days for 20 minutes each day, this was explored. In addition, we investigate the impact of LIPUS on a variety of senescent indicators, including cell shape, senescence-related b-galactosidase activity, foci of DNA damage associated with senescence, and p21WAF1/CIP1, a cyclin-dependent kinase inhibitor. As well as screening ofaging, secreted protein. Our experiments have produced encouraging results. We observe morphological changes in HFF cells following LIPUS stimulation. In HFF cells treated with cisplatin and stimulated with LIPUS, the b- galactosidase activity was markedly decreased. Cells treated with both cisplatin and LIPUS saw decreased DNA damage, although this effect was not statistically significant. Moreover, in cisplatin- treated cells exposed to LIPUS stimulation, the protein level of p21WAF1/CIP1 was similarly significantly downregulated. Regrettably, we were unable to find any effect for SASP released proteins after LIPUS activation on cells treated with cisplatin. It's interesting that following LIPUS stimulation, we could see a difference in secreted proteins of HFF cells. It might be as a result of the presence of replicative cells in the population of these cells. In conclusion, LIPUS may be a safe, non-invasive therapy for diseases associated with aging. which will enhance senior citizens' quality of life. We observed that this approach had a favourable impact on fibroblast senescence. Which, after more research, might be a viable senescence target therapy or a novel chemotherapy combo to shield normal cells from the harm these medications might otherwise cause.