Magnetic Field Changes Macrophage Phenotype.

Macrophages play a crucial role in homeostasis, regeneration, and innate and adaptive immune responses. Functionally different macrophages have different shapes and molecular phenotypes that depend on the actin cytoskeleton, which is regulated by the small GTPase RhoA. The naive M0 macrophages are slightly elongated, proinflammatory M1 are round, and M2 antiinflammatory macrophages are elongated. We have recently shown in the rodent model system that genetic or pharmacologic interference with the RhoA pathway deregulates the macrophage actin cytoskeleton, causes extreme macrophage elongation, and prevents macrophage migration. Here, we report that an exposure of macrophages to a nonuniform magnetic field causes extreme elongation of macrophages and has a profound effect on their molecular components and organelles. Using immunostaining and Western blotting, we observed that magnetic force rearranges the macrophage actin cytoskeleton, the Golgi complex, and the cation channel receptor TRPM2, and modifies the expression of macrophage molecular markers. We have found that the magnetic-field-induced alterations are very similar to changes caused by RhoA interference. We also analyzed magnetic-field-induced forces acting on macrophages and found that the location and alignment of magnetic-field-elongated macrophages correlate very well with the simulated distribution and orientation of such magnetic force lines.

Fisetin protects against high fat diet-induced nephropathy by inhibiting inflammation and oxidative stress via the blockage of iRhom2/NF-κB signaling.

Promoted inflammation enhances the development of nephropathy in obesity. Fisetin (3,3',4',7-tetrahydroxyflavone, FIS) is a naturally occurring dietary flavonoid, and exhibits anti-inflammatory and anti-oxidative properties. Inactive rhomboid protein 2 (iRhom2), an inactive member of the rhomboid intramembrane proteinase family, is an essential inflammation-associated regulator. Here, we attempted to investigate the protective mechanisms of FIS against high fat diet (HFD)-induced nephropathy, with particular focus on iRhom2. We found that HFD induced systematic and renal pro-inflammatory cytokine production. Furthermore, iRhom2 expression was markedly elevated in kidney of HFD-fed mice, and in PAL-incubated macrophages, accompanied with high phosphorylation of NF-κB. Significant oxidative stress was observed in kidney of HFD-fed mice through suppressing Nrf-2/HO-1 signaling. Moreover, activation of iRhom2/NF-κB signaling and oxidative stress by PAL was detected in macrophages, which were effectively reversed by FIS. Importantly, we showed that iRhom2 knockdown significantly abrogated the ability of FIS to restrain inflammation and oxidative stress induced by PAL in macrophages, indicating that iRhom2 might be a potential therapeutic target for FIS during nephropathy treatment. Together, these results revealed that FIS could mitigate HFD-induced renal injury by regulating iRhom2/NF-κB and Nrf-2/HO-1 signaling pathways.

Transsphenoidal surgery assisted by a new guidance device: results of a series of 747 cases.

OBJECTIVE: The objective of this study is to report the efficacy and safety of microsurgical transsphenoidal surgery using a frame for sella guidance in a series of patients with untreated pituitary adenoma. METHODS: In this study, seven hundred and forty-seven patients undergoing transsphenoidal resection of a pituitary adenoma involving use of the frame were included. Follow-up of twelve to one hundred months was performed in all patients. RESULTS: During the procedures using the frame, pituitary adenomas were fully exposed, and no cavernous sinus haemorrhage due to anteroposterior displacement or internal carotid artery lesion due to right-and-left deviation occurred. The duration of the surgical procedure ranged from 28 min to 87 min with a mean of 44 min. The most frequent tumour type was prolactin-secreting adenoma (32.4%), followed by clinically non-functioning adenoma (NFPA) (28.5%), growth hormone-secreting adenoma (25.0%), and adrenocorticotropin-secreting adenoma (13.7%). Normalisation of visual defects occurred in 226 (42.2%) of the 535 patients with visual disturbances. Normalisation of hormone occurred in 458 of 551 patients with endocrine-active tumour in the follow-up period. Two patients died as a consequence of surgery. CONCLUSION: The endonasal transsphenoidal technique is a safe, quick, and effective approach to pituitary adenomas. Our guidance frame allows the surgeon to open and close the wound rapidly, which avoids trajectory deviation and shortens the duration of the surgical procedure.