BackgroundTraumatic brain injury (TBI) is characterized by cognitive deficits, which was associated with brain oxidative stress and apoptosis. Resveratrol (RSV) is an anti-apoptotic and anti-oxidative. This study aimed to investigate neuroprotective effects and involved molecular mechanisms in TBI.Material/MethodsRSV and p38 inhibitor were administrated to TBI rats. Cognitive deficits were evaluated by Morris water maze assay. Reactive oxygen species (ROS) and apoptosis were detected in rat brains by fluorescent staining. Western blotting was used to assess the phosphorylation of p38 and the expression levels of Nrf2, HO1, and activated caspase-3.ResultsRSV administration attenuated cognitive deficits of TBI rats. The ROS generation and apoptosis in the brain of TBI rats were suppressed by RSV treatment. Moreover, RSV treatment recovered activation of p38/Nrf2/HO1 signaling pathway. The co-administration of p38 inhibitor impaired RSV’s attenuating effects on cognitive deficits, brain apoptosis, and ROS generation.ConclusionsRSV attenuated cognitive deficits of TBI by inhibiting oxidative stress-mediated apoptosis via targeting p38/Nrf2 signaling.

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Metastatic bone pain is characterized by insufferable bone pain and abnormal bone structure. A major goal of bone cancer treatment is to ameliorate osteolytic lesion induced by tumor cells. Corydalis saxicola Bunting total alkaloids (CSBTA), the alkaloid compounds extracted from the root of C. saxicola Bunting, have been shown to possess anticancer and analgesic properties. In this study, we aimed to verify whether CSBTA could relieve cancer induced bone pain and inhibit osteoclastogenesis. The in vivo results showed that CSBTA ameliorated Walker 256 induced bone pain and osteoporosis in rats. Histopathological changes also supported that CSBTA inhibited Walker 256 cell-mediated osteolysis. Further in vitro analysis confirmed that CSBTA reduced the expression of RANKL and downregulate the level of RANKL/OPG ratio in breast cancer cells. Moreover, CSBTA could inhibit osteoclastogenesis by suppressing RANKL-induced NF-κB and c-Fos/NFATc1 pathways. Collectively, this study demonstrated that CSBTA could attenuate cancer induced bone pain via a novel mechanism. Therefore, CSBTA might be a promising candidate drug for metastatic bone pain patients.

Rational: Reconstruction of complex craniofacial defects in fronto-orbital region has been reported to be extremely few. In this study, we report 2 cases with fronto-orbital defects of different etiologies in one-stage surgical reconstruction with polyetheretherketone (PEEK) prosthesis using computer-assisted design and computer-assisted manufactured (CAD–CAM) techniques. Patient concerns: One patient was a 49-year-old man, who admitted with a depressed and comminuted fracture in the left fronto-orbital region as a result of a motor vehicle collision. The other patient was a 45-year-old woman who was hospitalized with an unexpected diagnosis of a fronto-orbital bone tumor during a head CT examination in a minor traumatic brain injury. None of them had a significant past medical history. Diagnoses: The first patient's head computed tomography (CT) showed multiple depressed comminuted fractures in the right fronto-orbital region with localized frontal lobe contusion, and the diagnosis was clear when combined with the mechanism of traumatic head injuries. The second patient's head CT and magnetic resonance image suggested a right lateral orbital neoplastic lesion that distorted peripheral bone, the postoperative pathological examination demonstrated an osteoma with fibromatous hyperplasia, and thus the women's diagnosis was confirmed. Interventions: A three-dimensional image of both patients’ skull bone were collected from a high-resolution CT. A virtual surgical planning for lesion excision and defect remodeling based on CAD–CAM techniques was undertaken, and than the reconstruction surgery was performed in a single procedure using PEEK prosthesis. Antibacterial treatment was prescribed routinely. Outcomes: Postoperatively, both patients achieved excellent aesthetic restoration as well as functional recovery of the orbital cavity without neurological or infectious complications during an average 22 months follow-up. Lessons: The CAD–CAM PEEK implants could be a preferred option for reconstruction of patients with various complex fronto-orbital defects.

To elucidate regulatory effects and molecular mechanisms of diosgenin on colon cancer, this study administered diosgenin at concentrations of 10 (low), 50 (medium), and 100 μmol/L (high concentration group) at the cell level, respectively. EdU, colony formation, and Transwell assays were implemented to determine SW480 cellular proliferation and migration. Assays of flow cytometry and TUNEL were employed to estimate cell apoptosis. Additionally, nude mouse tumorigenesis assay was used to further verify the regulatory function of diosgenin on colon cancer. The target protein of diosgenin was predicted via molecular docking. The results showed that all three concentrations of diosgenin could reduce colon cancer cellular proliferation and migration, and after diosgenin treatment, colon cancer cellular apoptosis was markedly increased, and the 100 μmol/L diosgenin group produced the most satisfactory inhibition on colon cancer cell proliferation. Ki67 expression was markedly reduced whereas those of Bax and caspase3 were greatly increased after diosgenin treatment. The nude mouse tumorigenesis assay indicated that the parameters of tumorous volume and mass of diosgenin treatment group were greatly decreased as compared to control, and as the concentration of diosgenin increased, the inhibitory effect was more significant. Molecular docking indicated that STAT3 served as a target protein of diosgenin. Moreover, after diosgenin treatment on colon cancer cells, the STAT3 expression was markedly reduced. The STAT3 overexpression would counteract the inhibitory effect of 50 μmol/L diosgenin in both suppressing colon cancer cellular proliferation and migration and promoting apoptosis. Taken together, all our outcomes demonstrated the diosgenin effects in not only inhibiting colon cancer cellular proliferation and migration but also promoting cancerous cellular apoptosis. Diosgenin is a regulatory player in targeting and regulating STAT3.