SGK1 may play an important role in macrophage recruitment and M2 macrophage activation by activating the STAT3 pathway, which leads to angiotensin II-induced cardiac fibrosis.
BackgroundMacrophages, the key component of the tumor microenvironment, are differentiated mononuclear phagocyte lineage cells that are characterized by specific phenotypic characteristics that have been implicated in tumor growth, angiogenesis, and invasion. CX3CR1, the chemoattractant cytokine CX3CL1 receptor, plays an important role in modulating inflammatory responses, including monocyte homeostasis and macrophage phenotype and function. However, the role of CX3CR1 in the regulation of the tumor inflammatory microenvironment is not fully understood.MethodsUsing in vivo hepatic metastasis model, human colon carcinoma specimens, immunohistochemical staining, TUNEL staining, flow cytometry analysis, Western blotting assay and co-culture in three-dimensional peptide gel, we determined the effects of CX3CR1 on angiogenic macrophage survival and tumor metastasis.ResultsIn this study, we found that CX3CR1 was expressed in human colon carcinomas in a histologic grade- and stage-dependent manner, and CX3CR1 upregulation in TAMs was correlated with poor prognosis. Furthermore, we showed that in a microenvironment lacking CX3CR1, the liver metastasis of colon cancer cells was significantly inhibited. The underlying mechanism is associated with decrease accumulation of angiogenic macrophages that can be partly attributed to increased apoptosis in the tumor microenvironment, thus leading to impaired tumor angiogenesis in the liver and suppressed tumor metastasis.ConclusionsOur results suggest a role of CX3CR1 in angiogenic macrophage survival in the tumor microenvironment contributing to tumor metastasis.
Background Corneal transplantation is a common surgical intervention for restoring vision loss due to corneal damages. However, for cultural reasons, there is a huge shortage of donor corneas in China. Acellular porcine corneal stromas (APCSs) can be used as corneal substitutes in lamellar keratoplasty for corneal ulcers. This study was conducted to analyze the results of APCS use for herpes simplex keratitis (HSK). Methods The study involved HSK patients who underwent keratoplasty with APCSs from February 2016 to October 2017 in the second affiliated hospital of Zhejiang University. Patient data were collected at 7 days, 1 month, 3 months, 6 months, and at the last follow‐up (7‐25 months) postoperative. The corneal transparency, neovascularization, visual acuity, and graft stability were observed. Results Thirteen patients with HSK including five patients with corneal perforation were included in this study, nine patients underwent deep anterior lamellar keratoplasty (DALK) and five perforation patients underwent double lamellar keratoplasty. There were nine men and four women with an average age of 62.5 ± 5.6 years old (ranging from 52 to 70 years old). The mean postoperative follow‐up duration was 15.1 ± 5.8 months (ranging from 7 to 25 months). At the last visit, visual acuity improved in nine patients (69.2%) compared with preoperative (P = 0.008).The grafts of seven individuals (53.8%) were completely transparent or slightly opaque; their corneal transparency score had improved significantly compared with before the surgery (P = 0.010). Various degrees of neovascularization were present in 11 of the 13 patients (84.6%), most neovascularization gradually stabilized. Graft dissolution occurred in three eyes (23.1%) during the observation period, two underwent regrafting, the other one became stable after treatment. Three patients underwent second allograft transplantation, two of which encountered APCS graft dissolution and one of the patients requested a human donor allograft transplantation due to transparency issues despite the absence of adverse issues. Conclusion Acellular porcine corneal stroma seems to be effective in the treatment of HSK and can be used in HSK with corneal perforation by using double lamellar keratoplasty in an emergency.
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