Articular cartilage degradation is prevented by tanshinone IIA through inhibiting apoptosis and the expression of inflammatory cytokines.

The present study aimed to investigate the effect of tanshinone IIA on the degradation of articular cartilage in a rat model of osteoarthritis (OA). The OA rat model was established by anterior cruciate ligament transection (ACLT) and medial meniscus resection (MMx). The animals were treated for 28 days with 0.25­0.5 mg/kg doses of tanshinone IIA following ACLT + MMx. The knee joints of the rats in the ACLT + MMx group exhibited marked alterations in articular cartilage histopathology and higher Mankin scores, compared with those in the normal group. Tanshinone IIA treatment at a dose of 0.5 mg/kg significantly inhibited cartilage degradation and improved Mankin scores in the OA rat model (P<0.002). Tanshinone IIA treatment completely inhibited the ACLT + MMx­induced accumulation of inflammatory cells and disintegration of synovial lining in the rats. An increase in the dose of tanshinone IIA between 0.25 and 0.5 mg/kg reduced the proportion of apoptotic chrondrocytes from 41 to 2% on day 29. Treatment of the rats in the ACLT + MMx group with 0.5 mg/kg doses of tanshinone IIA markedly inhibited the expression level of matrix metalloproteinase and increased the expression of tissue inhibitor of metalloproteinase in the rat articular cartilage tissues. Tanshinone IIA treatment significantly reduced the levels of inflammatory cytokines, including interleukin­1ß, tumor necrosis factor­α and nitric oxide in rat serum samples. The protein expression levels of bone morphogenetic protein and transforming growth factor­ß were significantly increased by tanshinone IIA in the ACLT + MMx rats. Therefore, tanshinone IIA inhibited articular cartilage degradation through inhibition of apoptosis and expression levels of inflammatory cytokines, offering potential for use in the treatment of OA.

A study on role of triiodothyronine (T3) hormone on the improvement of articular cartilage surface architecture.

The present study was aimed to investigate the effect of triiodothyronine (T3) on the improvement of articular cartilage surface architecture at in vitro level. The T3 hormone was applied to neo-tissues in the range of 50, 100, 150 and 200ng/ml for 5 weeks. At the end of the treatment, biochemical and histological evaluation was carried out in the neo-tissues. T3 hormone application significantly increased the collagen production in neo-cartilage tissues. The properties of tensile and compressive were significantly increased compared to the controls. However, T3 hormone application also induced hypertrophy. At the higher dose concentration of T3 hormone application, tensile and compressive properties were tremendously increased 4.3 and 4.6 fold respectively. Taking all these data together, it suggested that the T3 hormone application could be a potential agent to increase the functional properties such tensile and compressive in neo-tissues.

Physcion, a naturally occurring anthraquinone derivative, induces apoptosis and autophagy in human nasopharyngeal carcinoma.

AIM: Physcion is a major bioactive ingredient in the traditional Chinese medicine Radix et Rhizoma Rhei, which has an anthraquinone chemical structure and exhibits a variety of pharmacological activities including laxative, hepatoprotective, anti-inflammatory, anti-microbial and anti-proliferative effects. In this study we investigated the effect of physcion on human nasopharyngeal carcinoma in vitro and in vivo, as well as the mechanisms underlying the anti-tumor action. METHODS: The nasopharyngeal carcinoma cell line CNE2 was treated with physcion, and cell viability was detected using MTT and colony formation assays. Flow cytometry was used to assess the cell cycle arrest, mitochondrial membrane potential loss, apoptosis, autophagy and intracellular ROS generation. Apoptotic cell death was also confirmed by a TUNEL assay. The expression of target or marker molecules was determined using Western blotting. The activity of caspase-3, 8, and 9 was detected with an ELISA kit. A xenograft murine model was used to evaluate the in vivo anti-tumor action of physcion, the mice were administered physcion (10, 20 mg·kg-1·d-1, ip) for 30 d. RESULTS: Treatment with physcion (5, 10, and 20 µmol/L) dose-dependently suppressed the cell viability and colony formation in CNE2 cells. Physcion (10 and 20 µmol/L) dose-dependently blocked cell cycle progression at G1 phase and induced both caspase-dependent apoptosis and autophagy in CNE2 cells. Furthermore, physcion treatment induced excessive ROS generation in CNE2 cells, and subsequently disrupted the miR-27a/ZBTB10 axis, resulting in repression of the transcription factor Sp1 that was involved in physcion-induced apoptosis and autophagy. Moreover, physcion-induced autophagy acted as a pro-apoptotic factor, and possibly contributed to physcion-induced apoptosis. In the xenograft murine model, administration of physcion dose-dependently suppressed the tumor growth without affecting the body weight. Furthermore, the anti-tumor effects of physcion were correlated with downregulation of Sp1 and suppression of miR-27a in the tumor tissues. CONCLUSION: Physcion induces apoptosis and autophagy in human nasopharyngeal carcinoma by targeting Sp1, which was mediated by ROS/miR-27a/ZBTB10 signaling. The results suggest that physcion is a promising candidate for the treatment of human nasopharyngeal carcinoma.

The tumor-stroma ratio is an independent predictor for survival in nasopharyngeal cancer.

BACKGROUND: The tumor-stroma ratio (TSR) has been identified as a new and practicable prognostic histological characteristic of solid tumors. The aim of this study was to evaluate the prognostic value of the TSR in nasopharyngeal cancer (NPC). PATIENTS AND METHODS: A total of 93 patients who presented with NPC from 2004 to 2007 were studied. Radiotherapy with or without chemotherapy was administered according to their Union for International Cancer Control (UICC) stages. The TSR was assessed visually on hematoxylin and eosin-stained tissue sections of biopsy specimens by 2 independent observers. RESULTS: The 5-year overall survival (OS) and disease-free survival (DFS) rates were 66.67% and 54.91%, respectively, in the stroma-poor group and 40.48% and 33.33%, respectively, in the stroma-rich group. Both the 5-year OS and DFS rates in the stroma-poor group were significantly better than those in the stroma-rich group (p < 0.05). In a multivariate analysis, the TSR was identified as a highly significant prognostic factor for the 5-year OS (hazard ratio (HR) 1.999; p = 0.030) and the 5-year DFS (HR 1.925; p = 0.042). CONCLUSION: Stroma-rich tumors were associated with poor prognosis and an increased risk of relapse, which may serve as a new prognostic histological characteristic in NPC.

Treatment of osteonecrosis of femoral head with BMSCs-seeded bio-derived bone materials combined with rhBMP-2 in rabbits.

OBJECTIVE: To evaluate the effect of autologous bone marrow mesenchymal stem cells (BMSCs) seeded bio-derived bone materials (BBM) combined with recombinant human bone morphogenetic protein-2 (rhBMP-2) in repairing defect of osteonecrosis of femoral head (ONFH). METHODS: Early-stage osteonecrosis in the left hip was induced in 36 adult New Zealand white rabbits (provided by the Animal Center of Guangxi Medical University, Nanning, China) after core decompression and delivery of liquid nitrogen into the femoral head. Then the animals were divided into three groups according to the type of implants for bone repair: 12 rabbits with nothing (Group I, the blank control group), 12 with BBM combined with rhBMP-2 (Group II), and 12 with BMSCs-seeded BBM combined with rhBMP-2 (Group III). At 4, 8, and 12 weeks after surgery, X-ray of the femoral head of every 4 rabbits in each group was taken, and then they were killed and the femoral heads were collected at each time point, respectively. Gross observation was made on the femoral heads. After hematoxylin and eosin staining, Lane-sandhu scores of X-ray and bone densitometry were calculated and the histomorphometric measurements were made for the new bone trabeculae. RESULTS: At 12 weeks after surgery, two femoral heads collapsed in Group I, but none in Group II or Group III. X-ray examination showed that the femoral heads in Group I had defect shadow or collapsed while those in Group II had a low density and those in Group III presented with a normal density. Histologically, the defects of femoral heads were primarily filled with no new bone but fibrous tissues in Group I. In contrast, new bone regeneration and fibrous tissues occurred in Group II and only new bone regeneration occurrd in Group III. Lane-sandhu scores of X-ray, bone mineral density and rate of new bone in trabecular area in Group III were higher significantly than those of the other two groups. CONCLUSIONS: Our findings indicate a superior choice of repairing the experimental defect of ONFH with BMSCs- seeded BBM combined with rhBMP-2.