Uterine leiomyomas are the most common benign tumors of the female reproductive system. Obese individuals have a higher burden of uterine leiomyoma, yet the mechanism relating obesity and leiomyoma development remains unknown. In this study, we observe the effect of adipocyte coculture and leptin treatment on human myometrium and leiomyoma cells. We isolated primary leiomyoma and myometrium cells from hysterectomy or myomectomy patients. Protein expression levels of phosphorylated ERK1/2/total ERK1/2, phosphorylated STAT3/total STAT3, and phosphorylated AKT1/2/3/total AKT1/2/3 were quantified using immunoblotting in immortalized and primary leiomyoma and myometrial cells cocultured with human adipocytes and treated with leptin. An enzyme-linked immunosorbent assay (ELISA) was used to assess pro-inflammatory, fibrotic, and angiogenic factors in immortalized human myometrium and leiomyoma cells treated with leptin. The effects of STAT3, ERK, and AKT inhibitors were assessed in leiomyoma cell lines additionally cultured with adipocytes. Adipocyte coculture and leptin treatment increases the expression of JAK2/STAT3, MAPK/ERK, and PI3K/AKT signaling while inhibitors suppressed this effect. Leptin induces a tumor-friendly microenvironment through upregulation of pro-inflammatory (IFNγ, IL-8, IL-6, GM-CSF, MCP-1, and TNF-α), fibrotic (TGF-β1, TGF-β2, and TGF-β3), and angiogenic (VEGF-A, HGF, and Follistatin) factors in human leiomyoma cells. Furthermore, adipocyte coculture and leptin treatment increases leiomyoma cells growth through activation of MAPK/ERK, JAK2/STAT3, and PI3k/AKT signaling pathways. Finally, STAT3, ERK, and AKT inhibitor treatment suppressed PCNA, TNF-α, TGF-β3, and VEGF-A intracellular staining intensity in both adipocyte coculture and leptin treated leiomyoma cells. These findings suggest that, in obese women, adipocyte secreted hormone or adipocytes may contribute to leiomyoma development and growth by activating leptin receptor signaling pathways.
Objective: To examine public opinions of surgery in older adults. Background: Increasing numbers of older adults are undergoing surgery. National healthcare organizations recognize the increased risks of postoperative complications and mortality in the older surgical population and have made efforts to improve the care of older adults undergoing surgery through hospital-level programs. However, limited research has explored the opinions and responses of the wider U.S. public regarding surgery in older adults. Methods: We performed a qualitative, thematic analysis of reader comments posted in response to online newspaper articles relating to surgery in older adults. Articles were published in 2019-2020 and targeted for a popular press audience. Results: Nine hundred eight reader comments posted in response to 6 articles relating to surgery in older adults were identified. Articles were published in online editions of print newspapers with a digital circulation between 1.3 and 5.7 million subscribers. Three themes were identified: (1) wariness/distrust towards healthcare: including general distrust of medicine and distrust of surgery, (2) problems experienced: ineffective communication and unrealistic expectations, and (3) recommended solutions: the need for multidisciplinary teams and patient-centered communication. Conclusions: Overall, the public viewed surgery in older adults with wariness/distrust due to ineffective communication and unrealistic expectations. Specialized surgical care tailored to the unique needs of older adults is needed. The public perspective suggests that U.S. health systems should strongly consider adopting programs that provide care to meet the unique needs of older adults undergoing surgery and ultimately improve both patient outcomes and their surgical experience.
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