Cannabidiol promotes apoptosis of osteosarcoma cells in vitro and in vivo by activating the SP1-CBX2 axis.

Osteosarcoma is the most common primary malignant bone tumor that often occurs in children, adolescents, and young adults. Cannabidiol plays an essential role in cancer treatment. However, its effects on osteosarcoma have not yet been addressed. In the present study, we investigated the pharmacological effects of cannabidiol on osteosarcoma. We found that cannabidiol effectively suppressed the proliferation and colony formation of osteosarcoma cells. Further studies showed that cannabidiol significantly promoted cell apoptosis and changes in cell apoptosis-related gene proteins in vitro. In addition, cannabidiol administration inhibited tumor growth and promoted the apoptosis of osteosarcoma cells in a mouse xenograft model. The in vitro study also demonstrated that SP1 contributes to chromobox protein homolog 2 (CBX2) reduction in cannabidiol-treated MG63 and HOS cells, and that cannabidiol may recruit SP1 into the CBX2 promoter regions to downregulate CBX2 expression at the transcriptional level and promote osteosarcoma cell apoptosis. Further, the result showed that cannabidiol suppressed osteosarcoma cell migration. In summary, cannabidiol effectively promoted the apoptosis of osteosarcoma cells in vitro and in vivo and suppressed tumor growth in a mouse xenograft model by regulating the SP1-CBX2 axis. This finding provides novel therapeutic strategies for osteosarcoma in the clinic.

Pyroptosis is involved in the pathogenesis of human hepatocellular carcinoma.

Pyroptosis is a caspase-1 dependent programmed cell death, which is involved in the pathologic process of several kinds of cancers. Loss of caspase-1 gene expression has been observed in prostate and gastric cancers. However, the role of pyroptosis in human hepatocellular carcinoma (HCC) remains largely unknown. The aim of this study was to investigate the involvement of pyroptosis in the pathogenesis of HCC. Our study showed that pyroptosis was inhibited in HCC tissues and cells. Administration of berberine inhibited the viability, migration and invasion capacity of HepG2 cells through the induction of pyroptosis both in vitro and in vivo, which was attenuated by caspase-1 inhibitor Ac-YVAD-CMK. Conclusively, pyroptosis is involved in the pathogenesis of HCC, and may be a new neoplastic target for the treatment of HCC.

Impact of haze and air pollution-related hazards on hospital admissions in Guangzhou, China.

Guangzhou is a metropolitan in south China with unique pollutants and geographic location. Unlike those in western countries and the rest of China, the appearance of haze in Guangzhou is often (about 278 days per year on average of 4 years). Little is known about the influence of these hazes on health. In this study, we investigated whether short-term exposures to haze and air pollution are associated with hospital admissions in Guangzhou. The relationships between haze, air pollution, and daily hospital admissions during 2008-2011 were assessed using generalized additive model. Studies were categorized by gender, age, season, lag, and disease category. In haze episodes, an increase in air pollutant emissions corresponded to 3.46 (95 % CI, 1.67, 5.27) increase in excessive risk (ER) of total hospital admissions at lag 1, 11.42 (95 % CI, 4.32, 18.99) and 11.57 (95 % CI, 4.38, 19.26) increases in ERs of cardiovascular illnesses at lags 2 and 4 days, respectively. As to total hospital admissions, an increase in NO2 was associated with a 0.73 (95 % CI, 0.11, 1.35) and a 0.28 (95 % CI, 0.11, 0.46) increases in ERs at lag 5 and lag 05, respectively. For respiratory illnesses, increases in NO2 was associated with a 1.94 (95 % CI, 0.50, 3.40) increase in ER at lag 0, especially among chronic obstructive pulmonary disease. Haze (at lag1) and air pollution (for NO2 at lag 5 and for SO2 at lag3) both presented more drastic effects on the 19 to 64 years old and in the females. Together, we demonstrated that haze pollution was associated with total and cardiovascular illnesses. NO2 was the sole pollutant with the largest risk of hospital admissions for total and respiratory diseases in both single- and multi-pollutant models.

Nimodipine rescues N-methyl-N-nitrosourea-induced retinal degeneration in rats.

BACKGROUND: That nimodipine (NMD) is potentially useful for ophthalmic treatment. However, the effect of NMD is unknown on retinal degenerative diseases. OBJECTIVE: The purpose of the present study was to investigate the effect of NMD on N-methyl-N-nitrosourea (MNU)-induced retinal degeneration (RD) and elucidate its possible mechanisms. MATERIALS AND METHODS: Morphological observation of NMD on MNU-induced RD was evaluated by light microscopy and electron microscopy. Nonenzymatic antioxidant glutathione (GSH) was measured by a colorimetric method. Transforming growth factor-beta (TGF-ß) was measured by enzyme-linked immunosorbent assay (ELISA). Telomerase was detected by reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: The significantly protective effect of NMD on MNU-induced RD was demonstrated morphologically. NMD increased the content of GSH and decreased the level of TGF-ß in rat retina. RT-PCR analysis demonstrated that NMD treatment significantly decreased mRNA level of telomerase. CONCLUSION: These data suggest that NMD inhibit MNU-induced RD in rats. The expressions of TGF-ß, telomerase and GSH contents might partially contribute to its protective effects on MNU-induced RD.

Identification and detection of the isolated sinus venosus from the Asian toad.

The pacemaker activity of mammalian sinoatrial node (SAN) of the heart plays a fundamental role in the integration of vital functions. Studying factors such as drugs that influence pacemaker activity of SAN has its significance. In this study, we isolated sinus venosus, SAN from toads (Bufo gargarizans), and analysed its electronic signal, histological characteristics and the influence of acetylcholine (ACh) and ivabradine on its pacemaker activity using PowerLab® and Chart® 5.0 software. We found that when isolated sinus venosus was treated with ACh, its histological distribution was disorganized and inter-beat (RR) interval was also broadened. The high frequency normalized unit (HFnu) and Poincaré plot of heart rate variability (HRV) of the isolated sinus venosus was also altered upon ACh treatment in a time-dependent and dose-dependent manner. When treated with ivabradine, these parameters of HRV such as square root of the mean of the squared differences between adjacent NN intervals (RMSSD) and HFnu were in the upward tendency, but low frequency normalized unit and low frequency/high frequency were in the opposite tendency. Taken together, we have developed a new model for studying the influences of drugs on autorhythmicity using isolated sinus venosus of the toad. With this model, we showed that ACh and ivabradine may affect the pacemaker activity by stimulating muscarinic receptor or inhibiting If current, respectively.

[Teaching experience in integrated course of human development and genetics].

Establishment of integrated course system in human development and genetics is an important part of course reformation, and the improvement of this system is achieved by integrating the content of course, stabilizing teaching force, building teaching materials and applying problem-based learning. Integrity-PBL teaching model is founded and proved to be feasible and effective by teaching practice. Therefore, it maybe play an important role in improving teaching effect and cultivating ability of students to analyse and solve problems.

Ellagic acid promotes Abeta42 fibrillization and inhibits Abeta42-induced neurotoxicity.

Smaller, soluble oligomers of beta-amyloid (Abeta) play a critical role in the pathogenesis of Alzheimer's disease (AD). Selective inhibition of Abeta oligomer formation provides an optimum target for AD therapy. Some polyphenols have potent anti-amyloidogenic activities and protect against Abeta neurotoxicity. Here, we tested the effects of ellagic acid (EA), a polyphenolic compound, on Abeta42 aggregation and neurotoxicity in vitro. EA promoted Abeta fibril formation and significant oligomer loss, contrary to previous results that polyphenols inhibited Abeta aggregation. The results of transmission electron microscopy (TEM) and Western blot displayed more fibrils in Abeta42 samples co-incubated with EA in earlier phases of aggregation. Consistent with the hypothesis that plaque formation may represent a protective mechanism in which the body sequesters toxic Abeta aggregates to render them harmless, our MTT results showed that EA could significantly reduce Abeta42-induced neurotoxicity toward SH-SY5Y cells. Taken together, our results suggest that EA, an active ingredient in many fruits and nuts, may have therapeutic potential in AD.