Daphnoretin induces cell cycle arrest and apoptosis in human osteosarcoma (HOS) cells.

In this study antiproliferation, cell cycle arrest and apoptosis induced by daphnoretin in human osteosarcoma (HOS) cells were investigated. Antiproliferative activity was measured with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The IC(50) value of daphnoretin was 3.89 µM after 72 h treatment. Induction of apoptosis was evidenced by apoptotic body appearance and Annexin V-FITC/PI apoptosis detection kit. Flow cytometric analysis indicated daphnoretin arrested the cell cycle in the G2/M phase. Western-blot assay showed that the G2/M phase arrest was accompanied by down-regulation of cdc2, cyclin A and cyclin B1. Moreover, daphnoretin inhibited Bcl-2 expression and induced Bax expression to desintegrate the outer mitochondrial membrane and causing cytochrome c release. Mitochondrial cytochrome c release was associated with the activation of caspase-9 and caspase-3 cascade. Our results demonstrated that daphnoretin caused death of HOS cells by blocking cells successively in G2/M phases and activating the caspase-3 pathway.

lncRNA FER1L4 is dysregulated in osteoarthritis and regulates IL-6 expression in human chondrocyte cells.

Osteoarthritis (OA) is the most prevalent joint disease and is one of the major causes of disability in the world. There has been an increase in the incidence of OA, which is associated with an aging population, sedentary lifestyle, and reduced physical activity. Due to the complex OA pathogenesis, there are limited diagnostic tools. OA is a degenerative joint disorder with a recognized inflammatory component, usually described as abnormal expression of inflammatory factors. For instance, interleukin 6 (IL-6) has been shown to be upregulated in serum and synovial fluid among patients with OA. Most of the inflammatory factors have been associated with the expression of long noncoding RNAs (lncRNAs). However, the role of the novel lncRNA Fer-1-like protein 4 (FER1L4) in OA is yet to be determined. Here, we interrogated the expression profile of FER1L4 in patients with OA to define its potential application as a diagnostic marker. We collected synovial fluid and blood samples from both OA cases and normal controls. Using qRT-PCR, we evaluated the expression of FER1L4 in plasma and synovial fluid. On the other hand, the expression of IL-6 in plasma and synovial fluid was assessed using ELISA. Besides, the effect of age, gender or disease stage in the expression of the FER1L4 in plasma was also estimated. Moreover, the receiver operating characteristic (ROC) curves were used to determine the impact of FER1L4 in OA cases compared with the normal controls. In addition, we analyzed the correlation between FER1L4 and IL-6 through Pearson correlation analysis. Also, IL-6 expression in overexpressed FER1L4 samples was detected in chondrocytes through western blot analysis, while FER1L4 expression following endogenous IL-6 exposure was detected by qRT-PCR. Our data showed that whereas lncRNA FER1L4 is downregulated in OA patients, IL-6 is upregulated. The plasma FER1L4 levels among the OA cases were suppressed with disease progression and old age, and the down-regulation could efficiently discriminate OA patients from normal subjects. In addition, upregulation of FER1L4 inhibited IL-6 expression in human chondrocyte cells, and treatment with different concentrations of exogenous IL-6 did not affect the expression of FER1L4. Taken together, our data demonstrates that FER1L4 could efficiently identify OA cases from normal subjects, and can also modulate the expression of IL-6 in human chondrocytes.

Role of climate anomalies on decadal variation in the occurrence of wintertime haze in the Yangtze River Delta, China.

The wintertime haze day (HD) in the Yangtze River Delta (YRD) region of China shows a significant upward trend during the past decades due to the rapid industrialization and urbanization. Besides the enhanced anthropogenic emission, climate change also plays the important role in the long term HD variations. In this study, the significant decadal variation of wintertime HD during the period 1960-2012 in YRD is examined by the empirical orthogonal function (EOF) analysis, featured as less HD occurrence before 1980 and more occurrence after 2000. The numerical simulations by the global transport and chemical model (Model for Ozone and Related chemical Tracers, MOZART) with the same emission inventory suggest 8.4% enhancement of wintertime PM2.5 (particulate matter with the equivalent diameter of air dynamics less than or equal to 2.5µm) mass concentration in YRD during 2001-2009 compared with that during 1971-1979 attributed to meteorological changes, indicating the significant effect of climate anomaly on the decadal variations of wintertime HD. Through the composite analysis on the atmospheric dynamical and thermal conditions based on the reanalysis data, the faster warming in the lower and middle troposphere over the continent in the recent decade is suggested to be important for the out-of-phase decadal HD variation in YRD. The thermal anomaly not only reverses the zonal thermal difference of land-sea to stimulate the anomalous southerlies over YRD leading to reduced prevailing north wind in winter, but also develops the deep inversion below the mid-troposphere to enhance the atmospheric stability. As a result, more frequent and persistent air stagnations in recent decade are expected for the reduction of atmospheric horizontal dispersion and vertical diffusion capacity leading to more occurrence of wintertime HD in YRD.

Robust contribution of decadal anomalies to the frequency of central-Pacific El Niño.

During year-to-year El Niño events in recent decades, major sea surface warming has occurred frequently in the central Pacific. This is distinct from the eastern Pacific warming pattern during canonical El Niño events. Accordingly, the central-Pacific El Niño exerts distinct impacts on ecosystems, climate and hurricanes worldwide. The increased frequency of the new type of El Niño presents a challenge not only for the understanding of El Niño dynamics and its change but also for the prediction of El Niño and its global impacts at present and future climate. Previous studies have proposed different indices to represent the two types of El Niño for better understanding, prediction and impact assessment. Here, we find that all popularly used indices for the central-Pacific El Niño show a dominant spectral peak at a decadal period with comparatively weak variance at interannual timescales. Our results suggest that decadal anomalies have an important contribution to the occurrence of the central-Pacific El Niño over past decades. Removing the decadal component leads to a significant reduction in the frequency of the central-Pacific El Niño in observations and in Coupled Model Intercomparison Project Phase 5 simulations of preindustrial, historical and future climate.