Effect of α-tocopherol in alleviating the lipopolysaccharide-induced acute lung injury via inhibiting nuclear factor kappa-B signaling pathways.

Acute respiratory distress syndrome (ARDS) leads to the acute lung injury (ALI), a form of diffused alveolars injury, accompanied by severe inflammation and oxidative damage of alveolar epithelial cells. α-Tocopherol (α-TOH), one of the eight isoforms of vitamin E, is a natural antioxidant-free radical. We aimed to understand the effect of α-TOH and mechanism involved in inducing the ALI. Lipopolysaccharide (LPS) is injected into the trachea of mice to generate ALI mouse models. α-TOH was used to administrate the mice intragastrically to detect the expression of inflammatory factors and antioxidant molecules by enzyme linked immunosorbent assay, hematoxylin-eosin staining and immunohistochemical staining. Mouse alveolar epithelial cell line (MLE-12 cells) was used to determine the effect of α-TOH on alveolar epithelial cells. Inflammatory factors such as, interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α shows significant increase in the lung tissues of the mice induced by LPS and reduction in the expressions of superoxide dismutase (SOD)1/2 and glutathione peroxidase (GSH-Px). After treatment with α-TOH, the inflammation and oxidative stress levels shows substantial reduction in the lung tissues of the mice. Moreover, α-TOH also increases the proliferation ability of MLE-12 cells in vitro and reduces apoptosis level. In addition, α-TOH reduces p65 phosphorylation and nuclear translocation in alveolar epithelial cells in vivo and in vitro, thus, inhibiting the activity of the nuclear factor kappa-B (NF-κB) signaling pathway. α-TOH reduces the inflammation and oxidative stress of lung tissue by inhibiting the NF-κB signaling pathway, thereby alleviating the LPS-induced ALI.

Ball-Bearing-Inspired Polyampholyte-Modified Microspheres as Bio-Lubricants Attenuate Osteoarthritis.

Osteoarthritis, a lubrication dysfunction related disorder in joint, is characterized by articular cartilage degradation and joint capsule inflammation. Enhancing joint lubrication, combined with anti-inflammatory therapy, is considered as an effective strategy for osteoarthritis treatment. Herein, based on the ball-bearing-inspired superlubricity and the mussel-inspired adhesion, a superlubricated microsphere, i.e., poly (dopamine methacrylamide-to-sulfobetaine methacrylate)-grafted microfluidic gelatin methacrylate sphere (MGS@DMA-SBMA), is developed by fabricating a monodisperse, size-uniform microsphere using the microfluidic technology, and then a spontaneously modified microsphere with DMA-SBMA copolymer by a one-step biomimetic grafting approach. The microspheres are endowed with enhanced lubrication due to the tenacious hydration layer formed around the charged headgroups (-N+ (CH3 )2 - and -SO3- ) of the grafted poly sulfobetaine methacrylate (pSBMA), and simultaneously are capable of efficient drug loading and release capability due to their porous structure. Importantly, the grafting of pSBMA enables the microspheres with preferable properties (i.e., enhanced lubrication, reduced degradation, and sustained drug release) that are highly desirable for intraarticular treatment of osteoarthritis. In addition, when loaded with diclofenac sodium, the superlubricated microspheres with excellent biocompatibility can inhibit the tumor necrosis factor α (TNF-α)-induced chondrocyte degradation in vitro, and further exert a therapeutic effect toward osteoarthritis in vivo.

Reconstruct the proximal radius with iliac graft and elastic intramedullary nail fixation after tumor resection.

BACKGROUND: This study aims to introduce a novel technique in treating benign bone tumors of the proximal radius by elastic intramedullary nail fixation and iliac graft after tumor resection. METHOD: In this retrospective case series, the treatment outcomes of 17 patients with benign bone tumor involving the proximal radius were reported from January 2010 to August 2014. All the patients received reconstruction surgery with iliac graft and elastic intramedullary nail fixation after tumor resection. Pain scoring was assessed using the 0 to 10 numerical rating scale. The quality of life scoring was assessed using the SF-30 scoring system. In addition, functional outcome was assessed with the Musculoskeletal Tumor Society score and the Disabilities of the Arm, Shoulder, and Hand score. RESULTS: The mean follow-up was 16 months (range, 10-22). The average bone consolidate time was 19.2 weeks (range, 16-24 weeks). The pre- and postoperative pain scores were 5.47 ± 1.58 and 1.18 ± 0.39, respectively. The pain symptom was significantly ameliorated after the operation (t = 13.50, p < 0.01). The pre- and postoperative and the quality of life scores were 48.29 ± 6.58 and 77.47 ± 5.89, respectively; the quality of life score was dramatically improved (t = -20.11, p < 0.01). The mean Musculoskeletal Tumor Society score was 83.41 % (range, 63-93 %) and the mean Disabilities of the Arm, Shoulder, and Hand score was 14.1 (range, 5.8-38.3). CONCLUSION: Taken together, the application of iliac graft and elastic intramedullary nail fixation after excision of lesions might be associated to a significant reduction of the pain and improvement of QOL (quality of life) and limb function of patients with benign bone tumors of proximal radius.

Chromobox Homolog 4 is Positively Correlated to Tumor Growth, Survival and Activation of HIF-1α Signaling in Human Osteosarcoma under Normoxic Condition.

OBJECTIVES: The clinical significance and tumorigenesis of Chromobox homolog 4 (CBX4) have been reported in hepatocellular carcinoma. The purpose of this study is to confirm the expression, elucidate the biological function and investigate the potential mechanism of CBX4 in osteosarcoma (OS). METHODS: The expression of CBX4 in OS samples and cell lines was measured by RT-PCR and western blot test. Cell cycle, CCK8 and colony-forming assays were used to detect changes of cells growth. Cell apoptosis assay was used to measure cell survival capacity. Trans-well assay was used to test the activities of migration and invasion. The expression of genes regulated by CBX4 was detected by qRT-PCT test. RESULTS: The expression of CBX4 was up-regulated in multiple OS cell lines and clinical samples. Overexpression of CBX4 was correlated with advanced clinical stage, high degree of malignancy and low tumor necrosis rate. Moreover, knockdown of CBX4 resulted in significant inhibition of cell growth and cell survival in OS cells under normoxic condition. In addition, we found that knockdown of CBX4 lead to down-regulating of HIF-1α-targeted genes without changing HIF-1α expression itself. CONCLUSION: Taken together, CBX4 is up-regulated and has a pro-tumor effect in OS with an activation of HIF-1α signaling pathway under normoxic condition. Therefore, targeting CBX4 may provide a new therapeutic method for OS.

Efficacy of limb salvage with primary tumor resection simultaneously for solitary bone metastasis in limbs.

BACKGROUND: This study aims to evaluate the efficacy of limb salvage with primary tumor resection on patients with solitary bone metastasis. METHODS: A retrospective treatment outcome review was performed on 20 patients with solitary bone metastasis as the primary clinical symptom who were admitted to the hospital between 2006 and 2010. With primary tumor resection, 18/20 patients received limb salvage surgery simultaneously. Pain scoring was assessed using the 0 to 10 numerical rating scale. The quality of life scoring was performed before and 3 months after surgery using the SF-30 scoring system. In addition, limb function was assessed 3 months after the operation using the Scoring System of American Musculoskeletal Tumor Society system (MSTS). RESULTS: The pain symptom was significantly ameliorated after the operation (t=26.653, P<0.001), and the quality of life dramatically improved (t=-20.581, P<0.001). The postoperative MSTS scores ranged from 18 to 27. The average score was 23.10±2.36. The Kaplan-Meier analysis showed that no significant differences (χ2=1.589, P=0.207) were observed in the tumor-free survival time between the wide and marginal resections. CONCLUSIONS: The application of the wide or marginal excision for the primary lesion and bony metastasis focus, based on the principles of primary bone tumors, can significantly relieve the pain and improve the quality of life and limb function of patients whose solitary bone metastasis was manifested as the first sign.

Overexpression of X-Box Binding Protein 1 (XBP1) Correlates to Poor Prognosis and Up-Regulation of PI3K/mTOR in Human Osteosarcoma.

Increasing evidence demonstrates that dysregulation of XBP1 function contributes to tumorigenesis in some cancers. However, little is known about the role of XBP1 in the progression of osteosarcoma (OS). The expression of XBP1 in OS samples was measured by quantitative RT-PCR and Western blotting assays. Cell cycle analysis and cell counting kit 8 (CCK8) assays were performed to determine the effects of XBP1 expression on cells growth capacity. Cell apoptosis coassay was applied to determine cell survival. The expression of genes affected by XBP1 was examined by quantitative RT-RCR and validated by Western blotting assays. XBP1 was overexpressed in OS clinical samples compared with corresponding non-cancerous tissues. Overexpression of XBP1 was significantly associated with advanced clinical stages, high degree of malignancy and low tumor necrosis rate. Furthermore, hypoxia activated XBP1, and silencing XBP1 significantly enhanced OS cell apoptosis. Knock-down of XBP1 resulted in inhibition of OS growth. Most importantly, knockdown of XBP1 led to down-regulation of PIK3R3 and mTOR. Taken together, XBP1 is up-regulated and has a pro-tumor effect in OS with activation of PI3K/mTOR signaling. Thus, targeting XBP1 may provide a new potential therapeutic method for OS.

The long-term outcomes following the use of inactivated autograft in the treatment of primary malignant musculoskeletal tumor.

BACKGROUND: Biological reconstruction surgery is a tough but alluring option for treating primary malignant musculoskeletal tumors. In this article, we evaluate the clinical outcomes of primary malignant musculoskeletal tumors treated with inactivated autograft using alcohol. METHOD: In this article, we include 58 patients who had primary malignant bone tumors treated with wide resection and recycling autograft reconstruction using alcohol between January 2003 and January 2013. The outcomes were measured by recurrence, functional status, and complications. Functional status was assessed according to the Musculoskeletal Tumor Society Score (MSTSS). The Kaplan-Meier survival curve was used to evaluate the survival rate of the patient. RESULT: The most common tumor was osteosarcoma (31 cases) followed by chondrosarcoma (10 cases). The tibia was the most frequently involved skeletal site (27 cases) followed by femur (26 cases). The median follow-up period was 54 months, ranging from 18 to 96 months. In 58 patients, 12 were with local recurrence (20.7 %), 16 with lung metastasis (27.6 %), and 13 with complications (22.4 %). The main complication was infection (8 cases). The autografts survived in 49 patients (84.5 %). The mean MSTSS score was 78.5 %, ranging from 47 to 98 %. CONCLUSION: Recycling autograft reconstruction using alcohol had favorable clinical outcomes to some degree; however, the recurrence and complication rates seem to be high. Thus, we should apply this method with caution and choose the patients with strict surgical indication.