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Background The pathogenesis of silicosis is complex and treatment methods are limited. SiO2-induced increase of transforming growth factor-β1 (TGF-β1) can activate fibroblasts to promote collagen deposition, ultimately leading to fibrosis. Previous studies have confirmed that lipid metabolism plays an important role in the progression of silicosis. Peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α) mediates mitochondrial dysfunction and lipid metabolism pathways in diabetic models, but its role in silicosis has not been elucidated. Objective To investigate the effect of PGC1α on lipid metabolism disorder of macrophages induced by SiO2 and its effect on the progression of silicosis fibrosis. Methods (1) Macrophages were divided into four groups by transfecting and silencing PGC1α and its control sequence in macrophages and followed by SiO2 stimulation: negative control group (transfected with si-NC for 48 h), si-PGC1α group (transfected with si-PGC1α for 48 h), SiO2 stimulation group (stimulated with 50 μg·mL−1 SiO2 for 36 h after transfection with si-NC for 48 h), and si-PGC1α+SiO2 group (stimulated with 50 μg·mL−1 SiO2 for 36 h after transfection with si-PGC1α for 48 h). Western blot and cell immunofluorescence were used to test PGC1α expression, 4,4-difluoro-1,3,5,7,8-pentamethyl-4-bora-3a,4a-diaza-s-indacene (BODIPY 493/503) and total cholesterol (TC) and free cholesterol (FC) kits were used to test lipid accumulation, and the Oroboros2k-Oxygraph respiratory test system (O2K) was used to assess the effects of PGC1α on mitochondrial respiratory chain. ELISA kits were used to test TGF-β1 expressed in the macrophage supernatant. (2) Lung fibroblasts were divided into the same four groups as above, and stimulated with the supernatant of macrophages in the above groups. The expression of collagen Ι (COL Ι), E-cadherin (Eca), and fibronectin (FN) were detected by cell immunofluorescence and Western blot to further evaluate the effect of silencing PGC1α on fibrosis. Results The protein expression level of PGC1α stimulated by SiO2 was decreased, and the relative expression level of PGC1α was 0.78 times that of the control group (P<0.05). After transfection with si-PGC1α, the expression of PGC1α was decreased, and the relative protein expression level of the si-PGC1α group was 0.86 times that of the control group (P<0.05). Compared with the SiO2 stimulation group, the staining area of BODIPY 493/503 in the si-PGC1α+SiO2 group was enhanced, and the cholesterol-related indexes [TC, FC and cholesterol ester (CE)] were increased to 1.38, 1.10, and 2.26 times those in the SiO2 stimulation group (P<0.05). The activity of mitochondrial complex Ι was decreased, and the level of complex Ι in the si-PGC1α+SiO2 group was 0.63 times that in the SiO2 stimulation group (P<0.05). The secretion of TGF-β1 by macrophages increased, and the level of TGF-β1 in the si-PGC1α+SiO2 group was 1.15 times that of the SiO2 stimulation group (P<0.05). In addition, after stimulation of primary lung fibroblasts with macrophage supernatant, silencing PGC1α increased the expression levels of COL Ι and FN, while decreased the expression of Eca. The protein levels of COL Ι, FN, and Eca in the si-PGC1α+SiO2 group were 1.39, 1.18, and 0.82 times those in the SiO2 stimulation group, respectively (P<0.05). Conclusion Silencing PGC1α exacerbates SiO2-induced lipid metabolism disorder, inhibits mitochondrial respiratory chain, and aggravates the fibrosis induced by SiO2, suggesting that PGC1α may participate silicosis fibrosis by regulating mitochondrial respiratory chain and lipid metabolic disorder induced by SiO2.
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Objective@#: The surgical management of trigeminal neuralgia (TN) caused by petrous apex meningioma (PAM) is still a challenge because of the lesion’s deep location and the surrounding complex structures. The authors describe the intradural anterior transpetrosal approach (ATPA) and its effect on the treatment of TN secondary to PAM. @*Methods@#: A retrospective analysis of 15 patients with TN secondary to PAM who underwent surgery via the intradural ATPA was conducted. The key techniques, which included drilling off the petrosal apex (PA) and opening the upper wall of Meckel’s cave (MC), are described in detail. @*Results@#: Total removal of the tumor and complete pain relief (Barrow Neurological Institute I) were achieved in all 15 patients without significant morbidity. Five patients developed new facial numbness postoperatively, which disappeared within three months after surgery. The postoperative magnetic resonance imaging showed temporal lobe swelling in three patients, but no clinical symptoms. One patient had cerebrospinal fluid leakage and was managed with bed rest and temporary lumbar drainage. One patient had an intracranial infection and was treated with antibiotics. By the last follow up, no patients had pain relapse or/and tumor recurrence. It is worth noting that the vascular compression at the root of the trigeminal nerve was found in one patient during the operation. @*Conclusion@#: Our experience suggests that drilling off the PA and opening the upper wall of the MC are key elements for a good outcome of the treatment of TN secondary to PAM. The intradural ATPA has the advantages for both tumor resection and pain relief.