Intermittent cyclic mechanical compression promotes endplate chondrocytes degeneration by disturbing Nrf2/PINK1 signaling pathway-dependent mitophagy.

An abnormal mechanical load is a pivotal inducer of endplate cartilage degeneration, which subsequently promotes intervertebral disc degeneration. Our previous study indicated that intermittent cyclic mechanical compression (ICMC) promotes endplate chondrocyte degeneration, but the mechanism underlying this effect is unclear. In this study, we investigated PTEN-induced kinase 1(PINK1) dependent mitophagy during ICMC-induced endplate chondrocyte degeneration. Furthermore, we determined whether NF-E2-related factor 2 (Nrf2) activation correlated with PINK1-dependent mitophagy regulation and increased oxidation resistance of endplate chondrocytes under ICMC application. First, we generated a mechanical compression-induced endplate chondrocyte degeneration model in vitro and in vivo. ICMC was found to promote endplate chondrocyte extracellular matrix degradation. PINK1-mediated mitophagy was suppressed in the ICMC-stimulated endplate chondrocytes, while increased mitochondrial reactive oxygen species generation suggested that mitophagy is involved in the protective effect of mechanical strain on endplate chondrocytes. Moreover, Nrf2 expression, interaction with Kelch-like ECH-associated protein (Keap1), and nuclear translocation were inhibited by ICMC. Nrf2 overexpression inhibited reactive oxygen species production and reversed ICMC-induced endplate chondrocyte degeneration. Transfection with PINK1 shRNA abolished this effect and partially blocked Nrf2-induced mitophagy. Our findings suggested that ICMC could inhibit the Nrf2/PINK1 signaling pathway to reduce the mitophagy levels which significantly promote oxidative stress and thereby endplate chondrocyte degeneration. Therapeutic regulation of the Nrf2/PINK1 signaling pathway may be an efficient anabolic strategy for inhibiting this process.

Exposure of the hidden anti-ferromagnetism in paramagnetic CdSe:Mn nanocrystals.

We present theoretical and experimental investigations of the magnetism of paramagnetic semiconductor CdSe:Mn nanocrystals and propose an efficient approach to the exposure and analysis of the underlying anti-ferromagnetic interactions between magnetic ions therein. A key advance made here is the development of an analysis method with the exploitation of group theory technique that allows us to distinguish the anti-ferromagnetic interactions between aggregative Mn(2+) ions from the overall pronounced paramagnetism of magnetic-ion-doped semiconductor nanocrystals. By using the method, we clearly reveal and identify the signatures of anti-ferromagnetism from the measured temperature-dependent magnetisms and furthermore determine the average number of Mn(2+) ions and the fraction of aggregative ones in the measured CdSe:Mn nanocrystals.

Gamma Knife surgery for hemifacial spasm related to cerebellopontine angle tumors.

OBJECT: Most cases of tumor-related hemifacial spasm (HFS) are treated by open surgery. The authors report the effects of Gamma Knife surgery (GKS) on benign tumor-related HFS at a mean follow-up time of 84 months. METHODS: Between 2000 and 2011, 6 patients (5 women and 1 man) harboring single tumors of the cerebellopontine angle (4 meningiomas and 2 vestibular schwannomas [VSs]) and experiencing HFS underwent GKS as a primary treatment. The mean age of the patients at the time of radiosurgery was 52.7 years (range 45-60 years). The patients' tumors lay within the radiosurgical target area. In the 4 cases of meningioma, the mean radiosurgical treatment volume was 5.3 cm(3) (range 1.2-9.6 cm(3)), and the mean radiosurgical tumor margin dose was 14.1 Gy (range 12-18 Gy); in the 2 cases of VS, the treatment volume was 2.5 cm(3) in 1 patient and 11.2 cm(3) in the other, and the margin doses were 11.5 and 12 Gy, respectively. The mean duration of HFS symptoms was 15.5 months (range 3-36 months). RESULTS: The mean follow-up period was 84 months (range 40-110 months). Overall, 4 (66%) of the 6 patients experienced complete relief from HFS without medication after GKS and 1 patient obtained a good outcome. The mean time for improvement to be realized was 12.6 months (range 3-24 months). Only 1 patient failed to experience relief from HFS, and coincidentally, the tumor did not shrink in that case. In all 6 patients (100%), tumor growth was controlled at a mean follow-up of 56 months after GKS: in 5 patients the tumor had decreased in size and in the other patient the tumor size remained unchanged. No new neurological deficit was noted after GKS, and 1 patient with facial numbness reported improvement after tumor shrinkage. CONCLUSIONS: Gamma Knife surgery appears to be effective in treating benign tumor-related HFS and in controlling tumor growth. A reduction in tumor volume is related to spasm improvement. Although a time latency for spasm relief is associated with GKS, minimal side effects are expected.

Cooking oil fumes improve lung adenocarcinoma cell survival through c-IAP2 induction.

Cooking oil fumes (COF) exposure was demonstrated to be associated with lung cancer development in Taiwanese nonsmoking women. Previous studies identified Cox-2 overexpression and oxidative DNA damage in lung adenocarcinoma cells after exposure to COF. Involvement of COF in lung tumorigenesis may be associated with cell survival, as well as proliferation of lung adenocarcinoma. To test this hypothesis, A549, a lung adenocarcinoma cell line, was used, and MTT assay data showed that the cell viability of A549 was significantly increased in a concentration-dependent manner by COF treatment for 48 h. Flow cytometery results indicated that the proportion of A549 cell at S-phase was markedly increased after exposure of COF. To elucidate whether the anti-apoptotic c-IAP2 (IAP2) was involved in COF-improved cell survival, IAP2 protein levels was determined by Western blot, and the results showed it was significantly induced by COF in a concentration-dependent manner. Moreover, the suppression of BAY, a nuclear factor (NF)-kappaB binding inhibitor, or the COF-induced IAP2 protein levels indicated that NF-kappaB activation by COF may partly be involved in IAP2 induction. These results showed that the positive impact of COF on cell survival and proliferation of A549 lung tumor cells may be through an induction of IAP2 overexpression.